Review of Black Cumin for Metabolic Disorders

Black cumin (Nigella sativa, Ranunculaceae) seed is popular in the Middle East and Southeast Asia for treating diabetes, dyslipidemia, hypertension, and obesity. However, clinical evidence is inconclusive. The purpose of this systematic review was to evaluate the clinical and biochemical effects of black cumin on lipid profiles, glycemic factors, blood pressure, and anthropometric indices (weight, body mass index [BMI], and waist circumference), all of which are parameters of metabolic syndrome.

The following databases were searched from inception through June 2014: PubMed, Google Scholar, Thomson Reuters Web of Science, and Cochrane. The following medical subject headings (MeSH) and title/abstract (tiab) search terms were used: (“Nigella sativa” [MeSH] OR “black seed” [tiab] OR “black cumin” [tiab] OR “Kalonji” [tiab]) AND “Triglycerides” [MeSH] OR “Cholesterol” [MeSH] OR “Lipoproteins, LDL” [MeSH] OR “Lipoproteins, HDL” [MeSH] OR “Blood glucose” [MeSH] OR “Hemoglobin A, Glycosylated” [MeSH] OR “Blood pressure” [MeSH] OR “Body mass index” [MeSH] OR “Waist circumference” [MeSH]). The inclusion criteria were (1) published in English, (2) the effect of black cumin on clinical or biochemical parameters, and (3) clinical trial. The exclusion criteria were (1) animal studies, (2) review studies, (3) the effect of black cumin on unrelated blood or clinical parameters, (4) the effect of black cumin combined with other plants or exercise, and (5) duplicated studies.

A total of 515 articles were located, and 18 studies (with a total of 1531 subjects) met the inclusion/exclusion criteria. The studies were highly heterogeneous: five studies were randomized, double-blind, controlled studies; five studies had no control group, and eight studies were randomized controlled studies. Included patients were aged 18-65 years and had diabetes (n = 5 studies), metabolic syndrome (n = 7 studies), hyperlipidemia (n = 4 studies), hypertension/coronary disease (n = 2 studies), obesity (n = 1 study), or were healthy subjects (n = 4 studies). All treatments were oral and doses ranged from 200 mg/day to 5 g/day of seed extract (n = 2 studies), seed oil (n = 8 studies), or seed powder (n = 13 studies). Treatment duration ranged from two weeks to six months.

Table 1 summarizes the study findings. The authors note significant findings; however, they do not report whether the changes are compared with baseline or control. In Table 1, the column titled “overall effect” indicates which parameters had more evidence in favor of a significant improvement.

Table 1: Summary of Number of Studies with Significant Improvements in Measured Parameters

Number of Studies
Parameters Significant improvement No significant effect Overall effect (Yes/No)
Triglycerides 7 10 No
Total cholesterol 10 4 Yes
Low-density lipoprotein (LDL) cholesterol 11 3 Yes
High-density lipoprotein (HDL) cholesterol 6 10 No
Fasting blood sugar 13 3 Yes
Glycosylated hemoglobin 4 Yes
Blood pressure 4 5 No
Weight 2 6 No
BMI 2 6 No
Waist circumference 1 5 No

Based on the number of studies demonstrating a significant improvement, the evidence weighs more in favor of black cumin improving total cholesterol, LDL, fasting blood sugar, and glycosylated hemoglobin. Evidence does not support an effect of black cumin on blood pressure or anthropometric indices. A total of 10 studies evaluated safety. Two studies that treated subjects with 5 mL/day black cumin seed oil reported mild nausea that resolved after one week of treatment. Eight studies measured liver and kidney function and reported no adverse effects.

The authors conclude that black cumin should be “a complementary treatment protocol for many diseases, especially metabolic disorders.” However, even though the evidence leans more favorably in the direction of a benefit for some parameters, the heterogeneity of the studies must be taken into consideration. It would have been advantageous if the researchers conducted a meta-analysis to provide more scientific rigor to their analysis and conclusions. Recommendations for the effective dose or preparation cannot be gleaned from this analysis. More research is needed if black cumin is to be recommended as a treatment for patients with symptoms of metabolic syndrome.

Resource:

Mohtashami A, Entezari MH. Effects of Nigella sativa supplementation on blood parameters and anthropometric indices in adults: A systematic review of clinical trials. J Res Med Sci. 2016;21:3. doi: 10.4103/1735-1995.175154.

 

Black Chokeberry—Bioactivities of Phenolic-rich Fruit May Contribute to Prevention of Chronic Diseases

Bioactive plant-derived compounds, especially phenolics with high antioxidant activity, are increasingly shown to be beneficial in preventing and treating chronic diseases. Black chokeberry (Aronia melanocarpa, Rosaceae) fruit has high levels of antioxidants, especially anthocyanins in the form of cyanidin derivatives. Black chokeberry fruit also contains other beneficial compounds such as vitamins C and E, carotenoids, pectins, and organic acids, as well as essential minerals (potassium, calcium, and magnesium).

Black chokeberry is native to eastern North America, from the Great Lakes to New England and higher altitudes of the Appalachians. Its fruits were used by Native Americans to treat colds. Introduced to Russia in the early 1900s, black chokeberry soon spread throughout the country, and in the early 20th century was introduced to other European nations, especially in Eastern Europe and Scandinavia. Several cultivars with larger and sweeter fruit have been developed in Northern and Eastern Europe, of which two, “Viking” and “Nero,” are available in the United States. A high tannin level and astringent taste limit black chokeberry’s popularity as a fresh fruit. It is widely used as a food colorant and flavoring; in teas (infusions), juices, jams, purees, etc.; and as a source of compounds for nutritional supplements. Its pomace is rich in bio-actives.

The authors summarize black chokeberry fruit’s composition and the bioavailability, antioxidant properties, and health-promoting benefits of its compounds in relation to chronic diseases. They do not describe search methods for the information presented.

Polyphenols are the major bioactive compounds of black chokeberry. These dietary antioxidants can scavenge free radicals, a cause of oxidative stress, which causes chronic inflammation and thereby increases the risk of diseases including atherosclerosis, cancer, and neurodegenerative conditions. Black chokeberry fruit’s total phenolic (TP) content is in the range of 690-2560 mg gallic acid equivalents (GAE) per 100 g fresh weight. This is higher than for many better-known berry crops, including blueberry (Vaccinium spp., Ericaceae), red raspberry (Rubus idaeus, Rosaceae), red currant (Ribes rubrum, Grossulariaceae), strawberry (Fragaria × ananassa, Rosaceae), “blackberry” (Rubus fruticosus; also a generic common name for an edible fruit produced by many Rubus spp.), and cranberry (V. macrocarpon), and comparable to the TP content of bilberry (V. myrtillus) and hawthorn (Crataegus monogyna, Rosaceae) fruit. As in other phenolic-producing plants, black chokeberry’s TP content and levels of specific phenolic compounds vary with cultivar and genotype, growth conditions, maturity at harvest, extraction and/or processing methods, and storage. The highest levels of phenolic compounds are found in the “Hugist” cultivar; the lowest, in “Aron.” The average concentration of phenolics in pomace is about five times that in black chokeberry juice. The most important phenolic compounds in black chokeberry fruits are phenolic acids, especially hydroxycinnamic acids, and flavonoids, including flavonols (epicatechin), flavonols (mainly quercetin glycosides), anthocyanins, and proanthocyanidins. While intestinal absorption of black chokeberry polyphenols is very poor, metabolization into other compounds allows for their beneficial effects. Quantities and proportions of individual phenolics vary among cultivars and plant parts and are affected by extraction/processing and storage methods. The relative antioxidant activities of different extracts and products are detailed. Compared with black chokeberry cultivars “Viking” and “Aron,” purple chokeberry (Aronia × prunifolia) dried berries had higher antioxidant activity. It is noted that black chokeberry’s lipophilic antioxidant capacity is quite low. It’s hydrophilic antioxidant capacity, along with black currant (Ribes nigrum) and elderberry (Sambucus spp., Adoxaceae), is among the highest of berry fruits.

Black chokeberry exerts anti-inflammatory, anti-atherosclerotic, hypotensive, anticoagulant, antithrombotic, and antiplatelet activities, making it especially valuable for cardiovascular health. It also has immunomodulatory, antiviral, and antibacterial effects. Black chokeberry extract decreases the expression of genes for cholesterol synthesis, uptake, and efflux dose-dependently in humans. It is known for its gastroprotective effects, especially against peptic ulcer, and for its antidiabetic effects, improving fasting glucose and lipid profiles. Anthocyanins may help prevent obesity and, by inhibiting α-glucosidase and α-amylase activities, reduce postprandial hyperglycemia. Aronia spp. extracts benefit risk factors related to insulin resistance, modulating multiple associated pathways. Black chokeberry anthocyanins can normalize carbohydrate metabolism. The anticancer effects of black chokeberry also operate through numerous pathways and mechanisms, including induction of detoxication enzymes, induction of cell cycle arrest apoptosis, and changes in cellular signaling. In vitro, it retards or halts the growth of human breast, leukemia, colon, and cervical cancer lines. Black chokeberry may reduce oxidative stress in patients with cancer before and after surgery. Different extracts and polyphenolic compounds may affect different cancer cell lines more or less strongly. Overall, black chokeberry, like other less-utilized berry crops, offers many positive benefits for prevention and treatment of chronic diseases. While some human trials are mentioned, more research is clearly warranted.

Resource:

Jurikova T, Mlcek J, Skrovankova S, et al. Fruits of black chokeberry Aronia melanocarpa in the prevention of chronic diseases. Molecules. June 7, 2017;22(6):944. doi: 10.3390/molecules22060944.

Review on the Therapeutic Effects of Aloe spp.

Aloe species’ (Xanthorrhoeaceae) leaf pulp has been used in Iranian traditional medicine (ITM) dating back to the eighth century CE. The genus has 446 species, with aloe vera (Aloe vera, Xanthorrhoeaceae) the most commonly used and studied. Aloe spp. grow wild in tropical regions of the world but only a few species have been commercially cultivated. Aloe spp. are grown for health foods, medicines, cosmetics, and decoration. Products include inner leaf gel and a bitter yellow latex (also called aloe juice) from peripheral bundle sheath cells just under the leaf surface.* Aloe leaf pulp is about 98.5% water but also contains at least 75 other compounds. The majority of these are mannose-based polysaccharides, and to a lesser extent, anthraquinones/anthrones, carbohydrates, chromones, phenolics, enzymes, and water- and fat-soluble vitamins, minerals, proteins, and organic acids. Aloe-emodin, an anthraquinone in Aloe latex, has been well studied. Aloin, aloesin, aloenin, and aloeresin are also unique Aloe compounds. The authors explored ITM texts for references to Aloe spp. and compared uses found there with modern pharmacological studies. They do not describe their literature search.

In the 17 ITM texts reviewed, Aloe spp. are described as hot and dry in temperament; and in most, as strong laxatives (for bile, yellow bile, and phlegm), and drying, fattening, soporific, warming, relaxing, resolving, cleansing, and bitter agents. ITM uses are categorized by the organs or physical systems involved. These include liver- and kidney-protective effects, supported for both aloe vera and candelabra aloe (A. arborescens) by pharmacological studies, with most attention paid to the species’ anti-inflammatory, antioxidative, antifibrotic, and lipid-modifying effects. A review of candelabra aloe reported it most active in treating liver diseases, especially cancers. Aloe‘s uses for gastrointestinal (GI) problems are among the most reported in the traditional literature, with preparations prescribed for many stomach ailments and loss of appetite. Powdered Aloe leaf pulp also was mentioned for GI problems. Hemorrhoids, constipation, helminthic infestations, flatulence, and anal fissures were treated with Aloespp. However, Aloe treatment was contraindicated in some cases of hemorrhoids or anal fissures and could cause hemorrhage by relaxing the rectal veins. ITM often used Aloe spp. with other herbs for intestinal diseases to prevent excess dryness. Preclinical studies support the use of aloe vera and its compounds for colitis, intestinal polyps, irritable bowel syndrome, and stomach ulcers, among others. An aqueous extract of bitter aloe (A. ferox) was a potent laxative in vivo.

In the upper respiratory tract, ITM used Aloe spp. especially for asthma, via inhalation of burned leaf smoke. They were also used for mouth, nose, tongue, and gum diseases. Polysaccharides and glycoprotein fractions of Aloe are reported to improve peripheral phagocytosis, supporting the traditional use for asthma. Bioaron C® (Phytopharm Klęka S.A.; Nowe Miasto nad Wartą, Poland), an herbal medicine made with an aqueous extract of candelabra aloe, was effective against influenzas A and B and other viruses in vitro. This product also showed significant antimicrobial and antifungal activity in vitro in another study. It is the only commercial product among the many studies of Aloe spp. these authors cite. In mice, an aloe vera gel extract showed promise in modulating tobacco (Nicotiana tabacum, Solanaceae) smoking-induced changes in pulmonary tissue. Extracts of aloe vera and bitter aloe are reported to act against herpes simplex viruses 1 and/or 2 in vitro, supporting ITM use of Aloe spp. for many genitourinary diseases, particularly genital ulcers and lesions.

Most ITM books investigated report Aloe‘s uses in cleansing the brain of waste humors (yellow bile and phlegm) and warming the brain. It was used for depression, schizophrenia, obsession, and headache; to strengthen mental acuity and for insomnia. Pharmacological studies of Aloe spp. and their extracts report hypnotic, peripheral analgesic, and neuroprotective effects. Improvements in memory, learning, cognitive function, and a potential anti-Parkinson’s disease effect also have been reported. A candelabra aloe extract was “a potent agent” in vitro in an Alzheimer’s disease model. Anticonvulsant activity, mitochondrial protection, and a protective effect against cerebral ischemia have all been reported in vitro or in vivo.

Preparations of Aloe spp. are used in ITM for skin problems from infections to allergies, wounds, malignant lesions, ulcers, bruises, and parasitic skin infestations. Aloe is a moisturizing agent, despite its dry nature, slowing evaporation of the skin’s moisture from sun and wind exposure. Skin protective activity seen in vitro and in vivo includes benefits in healing burn wounds (perhaps the best-known folk use for Aloe species globally); anti-infective and anti-allergic effects; and a significant increase in collagen. Raw mucilaginous gel of A. littoralis was reported to be a potential wound-healing and anti-inflammatory agent. Eyes and hair benefited from ITM applications of Aloespp. and extracts, borne out at least in part by preclinical studies. Socotrine aloe (A. perryi) and aloe vera were used in other in vitro and in vivo studies. ITM used Aloe spp. for arthralgia, gout, and other problems of the joints, muscles, and bones; no modern studies have explored these uses. Oddly, 35 clinical studies of Aloe spp. in conditions affecting several organ systems are relegated to a table and not discussed.

While Aloe spp. are generally considered safe, ITM scientists reported that they could harm the liver if overused, a toxicity reflected in a few modern case reports. These effects could be due to preparations and/or dosages used. Some species have toxic compounds, e.g., Yemen tree aloe (A. sabaea). Additional studies are certainly warranted to explore efficacy and dosage for a range of relevant conditions.

* However, beverages containing “aloe juice” contain only the liquefied gel, sometimes mixed with water or some citrus (Citrus spp., Rutaceae) juice, with the latex removed. Apparent differences in the chemical composition of aloe gel and latex are barely touched upon in this review.

Resource:

Akaberi M, Sobhani Z, Javadi B, Sahebkar A, Emami SA. Therapeutic effects of Aloe spp. in traditional and modern medicine: a review. Biomed Pharmacother. December 2016;84:759-772.

Review on the Effectiveness of Aloe Vera for Oral Diseases

The succulent leaves of the aloe vera (Aloe vera, Xanthorrhoeaceae) plant have been used medicinally for hundreds of years. The clear gel, or mucilage, found inside the leaves, is well known for having wound-healing, anti-inflammatory, antioxidant, antitumor, and analgesic properties. These attributes could potentially help in treating oral ailments. The aim of this systematic review was to accumulate and assess clinical trials evaluating the effectiveness of aloe vera preparations in treating various oral diseases.

Studies on aloe vera were eligible if they were randomized, controlled, single- or double-blind, cross-sectional, or case-controlled trials published as full papers in English. PubMed (Medline), Scopus, Cochrane Database, Embase, and ScienceDirect were searched from July 1998 to December 2015. Search terms included “herbs,” “Ayurveda,” and “oral mucosa.” The Jadad scale (a scale ranging from 0 to 5, where the higher number indicates higher trial quality) was used to assess quality.

In total, 15 articles met the inclusion criteria. Only six trials achieved a Jadad score of 4/5; the rest scored between 0 and 3. Most studies were carried out in hospital clinics in countries such as Iran, Spain, India, the United States, and Saudi Arabia. Study populations ranged from 20 to 110 patients with clinically diagnosed oral mucosal lesions. Five of the 15 studies focused on patients with oral lichen planus (OLP). Two studies examined efficacy on oral submucous fibrosis (OSMF) in patients. The remaining studies investigated the effects of aloe vera on burning mouth syndrome, radiation-induced mucositis, Candida-associated denture stomatitis, xerostomia, and minor recurrent aphthous/stomatitis. All studies demonstrated a low risk of bias using the Cochrane Risk of Bias Tool. Blinding bias was low among all studies except one on Candida-associated denture stomatitis. Randomization sequence bias was high in seven studies.

Most studies showed statistically significant results for efficacy of aloe vera in treatment of oral lesions. There were no withdrawals due to adverse effects of aloe vera in any of the clinical trials. This review found aloe vera was most beneficial in patients with OLP. All five studies in patients with OLP demonstrated a low risk of bias and proved aloe vera effectively reduced lesion-associated pain and burning sensation, leading to partial or complete remission of symptoms. Studies conducted in patients with OSMF showed aloe vera to be effective in all stages of OSMF, particularly mild-stage OSMF clinically and early-stage OSMF histopathologically. Pain and burning sensations were significantly reduced in OSMF studies, and other outcome measures (mouth opening, cheek flexibility, tongue protrusion) were promising. The overall quality of OSMF studies was good with low risk of bias. Four trials in patients with aphthous stomatitis were reviewed, consisting of 319 patients. The overall quality of these studies was good. Lesion healing improved and there was significant remission of pain, erythema, and lesion size. Aloe vera was found to be less beneficial in patients with radiation-induced mucositis, as it was not effective in improving tolerance to head and neck radiotherapy, decreasing mucositis, or decreasing soreness; however, quality-of-life measures were improved in the patients receiving aloe vera. In the single Candida study reviewed, aloe vera had an anticandidal oral effect surpassed by that of Triphala, an Ayurvedic combination remedy.

Lack of randomization, lack of double-blinding, and a lack of description for withdrawals, dropouts, and methods to generate the sequence of randomization were all prevalent limitations that excluded trials from this review. The studies included demonstrated aloe vera has a wide spectrum of properties and uses and is a promising agent in treating oral lesions. However, based on this review, aloe vera may be better suited to OLP, OSMF, and aphthous stomatitis lesions versus those induced by radiation or Candida. For aloe vera to be more seriously considered for clinical treatment of oral lesions, future clinical trials should strive to meet more rigorous standards.

Resource:

Nair GR, Naidu GS, Jain S, Nagi R, Makkad RS, Jha A. Clinical effectiveness of aloe vera in the management of oral mucosal diseases – A systematic review. J Clin Diagn Res. August 1, 2016;10(8): ZE01-ZE07. doi: 10.7860/JCDR/2016/18142.8222.

 

Artichoke Leaf Extract Shows a Potential Mild Benefit to Those with Metabolic Syndrome

Metabolic syndrome refers to a cluster of abnormalities such as hyperlipidemia, hyperglycemia, and obesity, and may lead to the development of diabetes and cardiovascular diseases. This condition is also associated with excess reactive oxygen species (ROS), and this redox imbalance is thought to correlate with further problems in metabolic syndrome. Artichoke (Cynara scolymus, Asteraceae) is consumed as a food and used medicinally for gastrointestinal problems. Artichoke leaf extract (ALE) has been shown to have beneficial effects for certain aspects of metabolic syndrome and is reported to have elevated antioxidant capacity. This double-blind, placebo-controlled, randomized, clinical trial investigated the potential effects of ALE intake on the oxidative stress and diet of patients with metabolic syndrome.

This study took place in Khoy, Iran, from November 2014 to May 2015. Metabolic syndrome was defined for this study as having 3 or more of the following: fasting blood sugar ≥ 100 mg/dL; triglyceride (TG) concentrations ≥ 150 mg/dL; blood pressure ≥ 130/85 mmHg; high-density lipoprotein cholesterol < 40 mg/dL for men or < 50 mg/dL for women; and waist circumference ≥ 95 cm (both men and women). Patients who wished to be in the study and were 20-50 years old were included. Those with systemic diseases such as diabetes, cancer, or Crohn’s disease, or those who, within the past 3 months, were consuming fish oil or antioxidant supplements, were taking pharmaceuticals for lipids or blood pressure or taking corticosteroids, were excluded. Also, those who smoked, were actively trying to lose weight, or had an allergy to artichoke, as well as women who were pregnant, lactating, or menopausal, were excluded.

The primary outcome of the study was any alteration in oxidative stress, with food consumption changes serving as the secondary outcome. The treatment and placebo were provided in tablet form by Dineh Pharmaceutical Company; Qazvin, Iran. ALE was prepared as a water-alcohol extract of leaves, standardized to contain 450 mg of a hydroalcoholic extract of artichoke leaf, with at least 4-5% chlorogenic acid. Placebo tablets contained corn (Zea mays, Poaceae) starch, lactose, and Avicel® (microcrystalline cellulose). Daily dosage was 4 tablets of either ALE (1,800 mg total) or placebo, with 1 tablet taken before breakfast and dinner, and 2 tablets taken before lunch. The total treatment duration was 12 weeks. Unused tablets served as a gauge of compliance. Patients were told not to alter their diet or exercise regimens and to report any adverse side effects.

Physical parameters (body mass index [BMI], weight, and waist circumference) and blood pressure were taken both at baseline and endpoint of the study. Physical activity was measured using the International Physical Activity Questionnaire, with results reported as high, moderate, and low, and dietary information was gathered using the software Nutritionist IV (First DataBank; San Bruno, California). Fasting blood was used for quantifying blood parameters; glutathione peroxidase and superoxide dismutase, both antioxidant enzymes, were measured in red blood cells, while total antioxidant capacity, TG, oxidized low-density lipoprotein (ox-LDL), and malondialdehyde concentrations, the latter both markers of oxidative stress, were measured in serum.

From 256 patients with metabolic syndrome, 80 were randomly assigned, with 40 patients in each group. In the ALE group, 7 patients were dropped from the study due to hypothyroidism or protocol violations, and 5 were dropped from the placebo group due to stopping the treatment or protocol violations; 33 patients in the ALE group and 35 in the placebo group finished the study. At baseline, no differences were seen between groups in any of the parameters, with 2 exceptions—in the placebo group, BMI was lower (P = 0.051) and diastolic blood pressure was significantly less (P = 0.030). Ox-LDL concentrations decreased significantly in those consuming ALE as compared with baseline (5,647.42 ± 1,031.93 ng/L vs. 5,914.28 ± 965.28 ng/L, P = 0.030). The decrease in ox-LDL across the study in the ALE group was also significantly greater as compared with that in the placebo group (−4.5% vs. −2.3%, P = 0.033). No other changes or differences in oxidative stress markers or enzymes were noted. No adverse side effects were observed.

The consumption of vitamin E and zinc significantly declined at the end of the study in the placebo group (P < 0.05 for both), and the amount of decrease in zinc consumption in the placebo group was significantly greater than that of the ALE group across the study (P = 0.019). In the ALE group, vitamin C consumption decreased, bordering significance (P = 0.061). Also, the percent decrease in TG concentrations was greater at the end of the study in the ALE group as compared with the placebo group (−17.74% vs. −5.02%, P = 0.010). No other parameters, including physical activity, were different from the study.

In conclusion, ALE consumption reduced ox-LDL as well as TG concentrations, indicating a potentially mild benefit to those with metabolic syndrome. As antioxidant status was unaffected in this study, oxidant status may have been acute or the oxidant stress too moderate to be detected. The authors suggest that the bioactivity observed may be due to compounds in ALE. There were some uneven physical parameters at baseline that may have influenced the outcomes reported here. Other discussed limitations include a short study duration and high amount of tablet consumption. Ideally, future studies will investigate the utility of ALE ingestion as an adjuvant for those with metabolic syndrome. The authors declare no conflict of interest.

Resource:

Rezazadeh K, Aliashrafi S, Asghari-Jafarabadi M, Ebrahimi-Mameghani M. Antioxidant response to artichoke leaf extract supplementation in metabolic syndrome: a double-blind placebo-controlled randomized clinical trial. Clin Nutr. March 23, 2017; [epub ahead of print]. pii: S0261-5614(17)30108-5. doi: 10.1016/j.clnu.2017.03.017.

Belladonna

Despite being a very poisonous plant, people have used belladonna in many different ways throughout history.

While it has been used as a poison in the past, scientists today extract chemicals from belladonna for use in medicine. These chemicals, when used under a doctor’s supervision, can treat a range of afflictions, from excessive urination at night to irritable bowel syndrome (IBS).

What is belladonna?

Belladonna plant
The belladonna plant may also be called deadly nightshade.

Belladonna (Atropa belladonna) is a poisonous plant, native to parts of Asia and Europe. It is sometimes known as deadly nightshade.

Belladonna produces small, black berries that must not be eaten. Eating the berries or leaves can be deadly. Similar to poison ivy, a person whose skin comes into direct contact with the leaves may develop a rash.

In ancient times, people used belladonna for its toxic properties, as an oral poison or on the tips of arrows.

Some scholars believe that Shakespeare referenced belladonna in his play, “Romeo and Juliet.” It is possible that Belladonna was the poison that Juliet drank to fake her death.

As time progressed, people used belladonna for cosmetic and medicinal purposes. For example, doctors used it as an antiseptic before surgery in medieval Europe.

During the Italian Renaissance, which lasted from the 14th to 16th century, fashionable women drank the juice of belladonna berries to dilate their pupils. Belladonna owes its name to this practice, as it means “beautiful woman” in Italian.

In modern times, optometrists often use belladonna to help dilate pupils when examining a person’s eyes.

Other recent uses of belladonna include over-the-counter creams and other herbal supplements. Despite its commercial availability, people are strongly advised to use belladonna with caution and under a doctor’s care.

belladonnaMedicinal uses

When used correctly in appropriate doses, belladonna is safe to use as part of regular medicinal practices.

It is important to note that ingesting even small amounts of the leaves or berries can be deadly. Small children and infants are, particularly at risk. Be sure to use caution when storing medicines that contain belladonna.

Scopolamine and atropine

Belladonna contains chemicals used to treat conditions such as irritable bowel syndrome.

Belladonna contains two chemicals used for medicinal purposes.

The first chemical is scopolamine, which is used primarily for reducing body discharges. It is also helpful in reducing stomach acid, which can help with both nausea and acid reflux.

Scopolamine is also used for controlling the heart rate and relaxing muscles.

The second compound extracted from belladonna is atropine. Similar to scopolamine, atropine can be used to help reduce bodily discharge, but it is not as effective as scopolamine when used as a muscle relaxant and in heart rate control.

Also, atropine can be used to dilate the eyes. In some cases, atropine works as an antidote to insect poison and chemical warfare agents.

Once extracted, one or both chemicals are combined with other medications to help treat some diseases and conditions.

Some of the treatments target:

  • motion sickness
  • irritable bowel syndrome
  • stomach ulcers
  • excessive nighttime urination
  • diverticulitis
  • Parkinson’s disease
  • pink eye

When taken as part of a prescribed medication, belladonna is considered mostly safe. Like all medicines, it can have side effects, and people should consider its use very carefully.

As with any potentially harmful medication, it is best to speak to a doctor before using a product containing belladonna.

Alternative medication

Like many well-known plants and extracts, belladonna is available in some over-the-counter alternative medications and supplements.

Unlike traditional medicines, the U.S. Food and Drug Administration (FDA) does not regulate supplements, which means they are often not tested for safety or the effectiveness of their claimed outcomes.

Companies that have made products containing belladonna state that it can improve various conditions. These include:

  • the common cold
  • fever
  • whooping cough
  • hay fever
  • earache
  • asthma
  • motion sickness
  • flu
  • a cough and sore throat
  • joint and back pain
  • arthritis pain
  • spasms, or colic-like pain in the stomach or bile ducts
  • nerve problems
  • gout
  • inflammation
  • Parkinson’s disease
  • hemorrhoids

Belladonna is an ingredient in creams, some liquids, ointments, and, in some cases, suppositories.

There is little research into belladonna’s effectiveness at treating any of the above conditions. It is important to consider the potential side effects before taking belladonna as a supplement.

Risks and side effects

Blurred vision and hallucinations are potential side effects of belladonna.

Belladonna is considered a toxic plant with historical uses as a poison. Despite being sold as an over-the-counter supplement, it is likely not safe to consume. It is also important to be aware that the FDA do not monitor the quality and purity of belladonna supplements.

There are some side effects to consider before using belladonna. These side effects include:

  • dry mouth
  • red, dry skin
  • inability to sweat
  • muscle spasms
  • blurred vision
  • enlarged pupils
  • hallucinations
  • inability to urinate
  • convulsions
  • seizures
  • coma

Women who are pregnant or breastfeeding may be at additional risk, as some of the belladonna’s side effects may appear in the unborn child, and it might dry up milk production.

In addition to the side effects, belladonna may make some conditions worse. These include disorders that some manufacturers claim Belladonna helps.

Conditions that belladonna can make worse include:

  • acid reflux
  • fever
  • rapid heartbeat
  • gastrointestinal (GI) tract infections
  • high blood pressure
  • constipation
  • urination problems

Belladonna has negative interactions with certain medications as well, such as those for allergies and depression. Side effects of the interaction include a rapid heartbeat and rashes.

Outlook

Belladonna can be a safe herbal supplement or part of medication but only when used properly under a doctor’s care and supervision. There are a number of side effects that should be considered before using belladonna as a supplement.

Additional research needs to be conducted to test the effectiveness of belladonna alongside the risks. Individuals should carefully consider their options before trying belladonna as a replacement or supplemental treatment.

Hibiscus Water Extract Demonstrates Significant Antioxidant Effects in Patients with Marfan Syndrome

Marfan syndrome (MFS) is an autosomal dominant genetic disorder manifesting in persistent oxidative stress and malfunction of connective tissue in the cardiovascular and skeletal systems. Previous studies of hibiscus (Hibiscus sabdariffa, Malvaceae) calyx drinks showed improvements in circulating antioxidant levels in healthy humans. Anthocyanins and organic acids like ascorbic acid are water-soluble antioxidants that are uncharacteristically rich in the hibiscus calyx, the ripened flowering body that is typically dark red in color. The goal of this prospective, observational, single-cohort study was to evaluate if a water infusion of hibiscus consumed daily could improve oxidative stress in patients with MFS.

The 3-month study took place at the National Institute of Cardiology Ignacio Chávez; Mexico City, Mexico. Seventeen patients with MFS and 10 healthy, control subjects were recruited through physical examination at the National Institute of Cardiology Ignacio Chávez. Additional echocardiography, computerized tomography, or magnetic resonance was done to ensure no aortic damage, and none of the enrolled patients were on anti-inflammatory medication.

Each patient consumed 1L daily for 3 months of a beverage made from boiling 20 g hibiscus calyces in a liter of boiling water (95-100°C) for 10 minutes, then left to cool. Hibiscus calyces were acquired in Chilapa de Álvarez (high zone from Guerrero, Mexico). Anthocyanins, flavonoids, and ascorbic acid (vitamin C) were estimated in the beverage by ultraviolet spectrometry, although composition data were not included in the study. Circulating levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GSHR), glutathione (GSH), lipid peroxidation (LPO) index, total antioxidant capacity (TAC), and ascorbic acid were measured in plasma from patients with MFS.

Levels of all oxidative stress markers were significantly different in patients with MFS versus control subjects. After 3 months of treatment, significant improvements in SOD (P = 0.03), GPx (P = 0.02), GST (P = 0.01), GSHR (P = 0.03), GSH (P = 0.05), LPO index (P = 0.001), and TAC (P = 0.04) were observed in patients with MFS. [Note: The P values in the abstract do not match those found in the text and figures.]

This study adds to existing clinical research on the antioxidant effects of hibiscus calyx beverages in humans. More research should be done to determine whether high-elevation hibiscus could have a different composition than other varieties. Admitted limitations include the small sample size, which was in large part due to the rarity of MFS (occurring in 2 or 3 individuals per 10,000). The long-term effects of hibiscus on slowing the progression of chronic disease related to oxidative stress should be investigated further.

Resource:

Soto ME, Zuñiga-Muñoz A, Guarner Lans V, Duran-Hernández EJ, Pérez-Torres I. Infusion of Hibiscus sabdariffa L. modulates oxidative stress in patients with Marfan syndrome. Mediators Inflamm. 2016;2016:8625203. doi: 10.1155/2016/8625203.

Valerian Root for Insomnia and Anxiety

Valerian is a plant with mild sedative properties that is sold as a sleeping aid and to treat anxiety. But does it work?

In the United States (U.S.), valerian dietary supplements are usually sold as sleeping aids. In Europe, people more often take them for restlessness and anxiety.

There are actually over 250 valerian species, but Valeriana officinalis is the one most commonly used for medicinal purposes.

While medicinal valerian dates back to ancient Greek and Roman times, strong clinical evidence for valerian’s effectiveness in treating insomnia and anxiety is lacking.

Still, Valerian is considered safe by the U.S. Food and Drugs Administration (FDA) and is gentler than synthetic drugs, such as benzodiazepines and barbiturates. For these reasons, valerian could be worth trying for anxiety or insomnia relief.

Potential benefits

Valerian root can potentially improve sleep quality and provide relief from anxiety.

Some possible benefits of valerian that have been reported by users include:

  • falling asleep faster
  • better sleep quality
  • relief from restlessness and other anxiety disorder symptoms
  • no “hangover effect” in the morning

However, stronger evidence is needed to be confident that valerian, and not some other factor, is responsible for these effects.

It is also necessary to determine whether a person’s insomnia and anxiety improvements are statistically significant.

Weaknesses in the studies

While there have been many studies exploring valerian’s effects, many of them have weaknesses that make their data unreliable.

Even with carefully controlled studies, it is still difficult to compare and combine data across studies. Some of the reasons for these problems include:

  • a small number of study participants
  • high rates of study participant withdrawal
  • wide variation across studies in methods of measuring sleep quality and anxiety relief
  • wide variation across studies in dosage and duration of valerian treatment
  • the severity of a person’s anxiety or insomnia is not well defined
  • flawed statistical analyses

Many of these issues are revealed in a review paper published in the American Journal of Medicine, which carefully analyzed the methods and data of 16 different valerian studies.

The paper produced conflicting results about the soundness of these studies. For example, one issue was that only six of the studies used similar methods to measure sleep quality, which meant that sleep quality improvement could not be compared across all studies.

Combined data shows improvements in sleep

woman's feet in bed
A combination of studies showed that valerian root may improve sleep quality significantly.

On the other hand, the combined data of these six studies did show a statistically significant improvement in sleep quality for the group of participants using valerian.

These studies also happened to have the largest sample sizes, perhaps giving them more strength than the others. Still, the authors of this review warn that the results should be taken with caution, as there were many flaws in their statistical analyses.

Studies look at a combination of herbs

A separate issue is that many studies do not explore the use of valerian alone, but instead analyze the effects of valerian combined with other medicinal herbs, such as passionflower or kava.

For example, another literature review analyzed 24 studies about the effectiveness of herbal supplements for anxiety. An individual study explored the impact of herbal supplements on insomnia in 120 participants.

Both found robust evidence for the effectiveness of supplements. However, it was hard to tell how responsible valerian was for these effects.

Larger, more statistically sound valerian-specific studies are needed to understand how well the supplement actually works in terms of treating insomnia and anxiety.

How valerian root works

Many researchers believe that it is not just one chemical that is responsible for valerian’s effects, but a combination of the plant’s components.

According to the National Institutes of Health, several of valerian’s chemical compounds have individually demonstrated sedative properties in animal studies.

It is also uncertain how valerian affects the brain. The most common theory is that valerian extract stimulates nerve cells to release a chemical called gamma-aminobutyric acid, or GABA.

GABA slows down nerve cell activity instead of exciting it.

Valerian extract may block an enzyme that destroys GABA, which means that more GABA is available for a longer amount of time.

All of these factors together might produce the calming effect that many who try valerian experience. Drugs such as Xanax and Valium also increase the amount of GABA in the body, and their effects are much greater than valerian.

Preparations

Valerian root can be consumed in many forms, including as a tea.

Valerian dietary supplements are usually made from the plant’s roots, but can also derive from its stems. Dried roots, other plant materials, or valerian extracts may be consumed in several forms, including:

  • teas
  • tinctures
  • capsules
  • tablets

The amount of valerian a person should take varies, but the dose typically ranges from 400-900 milligrams (mg) at bedtime.

The dosage may also depend on how much valeric acid the supplement contains. Valerenic acid is considered to be one valerian’s most powerful sedative components.

Herbalists advise only using valerian for 2-3 weeks and then taking a break for an equal length of time before starting up again. Herbalists recommend this break because some people who have used valerian for extended periods have reported adverse side effects, such as headaches, depression, or withdrawal after stopping.

Risks

The FDA (or other regulating agencies) do not monitor herbs and supplements for quality or purity. So, it is important to choose products from reliable sources. While further studies are needed to evaluate any potential long-term side effects, there have been very few reports of serious adverse events in connection to valerian.

According to the National Institutes of Health, the side effects most commonly reported by people involved in valerian clinical trials are:

  • headaches
  • dizziness
  • itchiness
  • gastrointestinal disturbances

However, these side effects cannot be directly attributed to valerian, as some of the people who were taking placebo supplements also reported side effects.

Despite valerian’s observed gentleness, women who are pregnant or breastfeeding are advised to avoid it because no studies have been carried out on the potential risks of valerian to a fetus or an infant.

Children under 3 years old should not be given valerian either as its effects on early development have not been evaluated.

Finally, a person must consult a doctor before using valerian if they are already taking:

  • benzodiazepines, such as Xanax, Valium, or Ativan
  • central nervous system depressants, such as phenobarbital or morphine
  • other sleep-aiding dietary supplements, such as kava or melatonin

The sedative and depressant properties of these drugs and supplements might combine with those of valerian, resulting in grogginess or more severe adverse effects.

Even if one is not taking any other medications, it is always a good idea to talk to a doctor before taking any supplements, including valerian.

African Plant Extract Offers New Hope for Alzheimer’s

A plant extract used for centuries in traditional medicine in Nigeria could form the basis of a new drug to treat Alzheimer’s disease, researchers at The University of Nottingham have found.

Their study, published in the journal Pharmaceutical Biology, has shown that the extract taken from the leaves, stem, and roots of Carpolobia lutea, could help to protect chemical messengers in the brain which play a vital role in functions including memory and learning.

The tree extract could pave the way for new drugs to tackle patient symptoms but without the unwanted side-effects associated with some current treatments.

The study was led by Dr. Wayne Carter in the University’s Division of Medical Sciences and Graduate Entry Medicine, based at Royal Derby Hospital. He said: “As a population, we are living longer, and the number of people with dementia is growing at an alarming rate. Our findings suggest that traditional medicines will provide new chemicals able to temper Alzheimer’s disease progression.”

Neurodegenerative diseases represent a huge health burden globally, placing pressure on health services and having a negative impact on the lives of patients and their families.

Researchers and drug companies are racing to discover new treatments for these disorders and have begun looking to plant extracts as a potential source of novel drugs.

In patients with Alzheimer’s disease and other diseases such as Parkinson’s disease and myasthenia gravis, the activity of the neurotransmitter acetylcholine, is reduced, leading to problems with memory and attention.

Current drugs – called acetylcholinesterase inhibitors – reduce the normal breakdown of acetylcholine. Extensive research is underway to find new versions of these drugs but with additional beneficial properties.

Carpolobia lutea, known more commonly as cattle stick, is a small shrub or tree found native to Central and West Africa. Herbalists in Nigerian tribes use the essence of the root as an aphrodisiac and the treatment of genitourinary infections, gingivitis, and waist pains.

It has also been reported to possess other anti-inflammatories, anti-arthritic, antimicrobial, antimalarial, and analgesic properties. This could be particularly important in Alzheimer’s disease as there is more evidence emerging that Alzheimer’s patients have inflammation in the brain.

The Nottingham study found that the plant was highly effective in preventing the breakdown of acetylcholine but had other beneficial antioxidant properties in fighting free radicals – unstable atoms that can cause damage to cells and contribute to aging and disease – damage that may be exacerbated in Alzheimer’s disease.

Article: Anti-acetylcholinesterase activity and antioxidant properties of extracts and fractions of Carpolobia lutea, Pharmaceutical Biology, doi: 10.1080/13880209.2017.1339283, published online 19 June 2017.

Lemon Balm Extract Reported Safe in Providing Beneficial Effects for Glycation-Associated Tissue Damage, Arterial Stiffness, and Skin Elasticity

  • Lemon Balm (Melissa officinalis, Lamiaceae)
  • Glycation-associated Tissue Damage
  • Arterial Stiffness
  • Skin Elasticity

Advanced glycation endproducts (AGEs) are generated by the nonenzymatic glycosylation of proteins, or glycation, and are associated with increased oxidative stress and inflammation. In patients with diabetes mellitus, cardiovascular disease, or Alzheimer’s disease, the tissue content of AGEs is much higher than in healthy individuals. The AGE pentosidine increases with age and correlates with the degree of skin and artery stiffness; yellowing skin associated with aging also may be due partly to glycation. Seeking to find a potent antiglycation food material, these authors studied plant extracts that inhibited the formation of pentosidine, selecting lemon balm (LB; Melissa officinalis, Lamiaceae) extract (LBE) and identifying its active components. In an open-label, parallel group, comparative trial, they examined the beneficial effects of LB on arterial stiffness, skin elasticity, and blood hematological and biochemical parameters.

A total of 681 plant extracts were screened and evaluated for antiglycation activity. Among the 22 possible candidate plants, 4 species were of the Lamiaceae family; 17 species exhibited higher activity against pentosidine than the antiglycation agent aminoguanidine. LB was selected from those plants because of its safety, taste, stable supply, and adaptability to beverage form.

Twenty-eight healthy Japanese subjects (14 males and 14 females) were enrolled in the trial, conducted at Yakult Central Institute in Tokyo, Japan, from late October 2010 to early December 2010. The subjects were instructed to continue their usual exercise regimens and diet, excluding herbal teas. The trial included a 1-week pre-intake phase and a 6-week intake phase. Measurements conducted during the pre-intake phase (baseline) and on the day after the last day of intake included brachial-ankle pulse wave velocity (baPWV) as a marker of arterial stiffness, blood pressure, skin elasticity of the left cheek, skin color, and hematological and biochemical parameters.

The subjects were randomly assigned to the LBE group or the control group, with 14 in each group. The beverages were prepared daily by the subjects for 6 weeks as follows: bags containing 3.3 g dried LB leaves (Charis Seijyo Co., Ltd.; Tokyo, Japan) in the LBE group or barley (Hordeum vulgare, Poaceae) tea grains (Nihon Seibaku Co., Ltd.; Kanagawa, Japan) in the control group were extracted for 5 minutes in 200 mL hot water before drinking. Fractionation of the LBE revealed that the polyphenol rosmarinic acid (RA) was the most abundant active component. The subjects recorded their daily intake of the beverages and any adverse effects.

Of the 14 subjects in the LBE group, 2 were excluded from the analysis because they had health problems, unrelated to the tea, for more than 10 days during the study period. Compliance rates were 100% in the control group and 99.5% in the LBE group.

Evaluations of the glycation-induced coloration of collagen fiber sheets and glycation-induced changes in the fibrous structure of elastin fiber sheets revealed that “LBE or RA dose-dependently suppressed glycation-associated reactions such as increased fluorescence, yellowing of collagen fiber sheets, and degeneration of the fibrous structure of elastin fiber sheets,” report the authors.

After 6 weeks of treatment, baPWV was reduced in the LBE group and unchanged in the control group, with a significant between-group difference in the change (P = 0.007). No significant between-group differences were observed for changes in systolic or diastolic blood pressure. Age of the subjects correlated strongly with baPWV at baseline (P < 0.001).

No significant between-group differences were observed in the changes in cheek skin elasticity during the trial. However, comparing the changes in male skin with female skin of both groups, the authors report that the only gender difference detected was a significant between-group difference in R7 value (total deformation) in only the female subjects; in females in the control group, the R7 value decreased by 0.044 ± 0.025 and in those in the LBE group, by 0.012 ± 0.018 (P = 0.027). The authors suggest that timing may have attributed to this finding, stating that because the trial was conducted during the autumn and winter, with frequent changes in humidity and temperature, and because female skin is thinner and drier than male skin, “the seasonal effects might be more severe in female subjects.”

In the LBE group compared with the control group, significant reductions were observed in both a* (red [asterisk is part of value name]; P = 0.017) and b* (yellow; P = 0.008) color values in forearm skin; the values did not change in the control group. Previously reported anti-inflammatory activity of RA1 may reduce a* value, say the authors. In one prior study, b* values increased through glycation in mouse skin,2 and such increases reportedly reflect the accumulation of AGEs.3,4 “Therefore, the decrease in b* values is presumed to be due to the anti-glycation effects of the daily intake of LB tea,” write the authors.

No significant between-group changes were observed for L* values (brightness of skin), which in earlier studies were found to be linked to antioxidation.5,6 “This observation indicates that the involvement of anti-oxidation in the anti-glycation effect of LB tea may be small,” state the authors.

No significant differences were seen in reported adverse effects between the 2 groups. Among the hematological and biochemical parameters, the serum glucose and uric acid levels after 6 weeks were significantly lower in the control group compared with baseline (P < 0.05 for both). Serum creatinine levels decreased significantly in both groups (P < 0.01 for the control group and P < 0.05 for the LBE group).

This study is limited by its small sample size; its lack of detection of AGE content in arteries and skin to clarify whether LB tea affects that content; and the study design, which did not include a placebo.

The authors conclude, “The hot water extract of LB leaves is considered a safe and potent food material to provide health benefits with regard to glycation-associated tissue damage and symptoms such as increased arterial stiffness and decreased skin elasticity.”

References

1Osakabe N, Takano H, Sanbongi C, et al. Anti-inflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its mechanism. Biofactors. 2004;21(1-4):127-131.

2Yokota M, Tokudome Y. Permeation of hydrophilic molecules across the glycated skin is differentially regulated by the stratum corneum and epidermis-dermis. Biol Pharm Bull. 2015;38(9):1383-1388.

3Monnier VM, Cerami A. Nonenzymatic browning in vivo: a possible process for the aging of long-lived proteins. Science. 1981;211(4481):491-493.

4Ohshima H, Oyobikawa M, Tada A, et al. Melanin and facial skin fluorescence as markers of yellowish discoloration with aging. Skin Res Technol. 2009;15(4):496-502.

5Kim SB, Jo YH, Liu Q, et al. Optimization of extraction condition of bee pollen using response surface methodology: correlation between anti-melanogenesis, antioxidant activity, and phenolic content. Molecules. 2015;20(11):19764-19774.

6Ya W, Chun-Meng Z, Tao G, Yi-Lin Z, Ping Z. Preliminary screening of 44 plant extracts for anti-tyrosinase and antioxidant activities. Pak J Pharm Sci. 2015;28(5):1737-1744.

Yui S, Fujiwara S, Harada K, et al. Beneficial effects of lemon balm leaf extract on in vitro glycation of proteins, arterial stiffness, and skin elasticity in healthy adults. J Nutr Sci Vitaminol (Tokyo). 2017;63(1):59-68.