Understanding plant to extract ratios in botanical extracts.

Dietary supplement current good manufacturing practice (cGMP) requires establishment of quality parameters for each component used in the manufacture of a dietary supplement to ensure that specifications for the identity, purity, strength, composition, and limits on contaminants are met. Compliance with botanical extract ingredient specifications is assured by using scientifically valid methods of analysis, the results of which are reported on certificates of analysis (CoAs). However, CoAs routinely include additional data that are not amenable to verification through methods of analysis. Such descriptive information may include Plant to Extract ratios, which are ratios of the quantity of botanical article used in the manufacture of the extract to the quantity of extract obtained. Plant to Extract ratios can be misleading when their meaning is not clearly understood. Plant to Extract ratios do not completely describe botanical extracts because other important factors influence the make-up of final extracts, such as the quality of the raw starting material (as can defined by pharmacopeial standards), extraction solvent(s) used, duration and temperature of extraction, and percentage and type of excipients present. Other important qualitative descriptions may include constituent "fingerprinting." Despite these issues, Plant to Extract ratios are often used as a measure of extract strength for dosage calculations. This article defines and clarifies the meaning of Plant to Extract ratios and their proper use in describing and labeling botanical extract ingredients and finished products containing them.

Buchu (Agathosma betulina and A. crenulata): Rightfully Forgotten or Underutilized?

Today, the term buchu refers to the two species in commerce, Agathosma betulina (P.J.Bergius) Pillans and Agathosma crenulata (L.) Pillans (Rutaceae). Its traditional use in urinary tract infections and related ailments made it a popular remedy, specifically in the US, in 19th century, but with the advent of antibiotics it became largely obsolete. Recent focus is on technological use and on the essential oil for use in the perfume and food-flavouring industry. A review of the scarce pharmacological research revealed moderate antimicrobial activity for a leaf extract but not the essential oil of both species in the MIC assay. In the 5-lipoxygenase (5-LO) assay the essential oil of both species revealed IC50 values of 50.37 ± 1.87 µg/ml and 59.15 ± 7.44 µg/ml, respectively. In another study 98% inhibitory activity was determined for 250 µg/ml of an ethanolic extract of A. betulina on cyclooxygenase (COX)-1 and a 25% inhibitory activity on COX-2. Analgesic activity of an ethanolic extract of A. betulina was shown in mice. Moderate antioxidant activity was determined for methanol:dichlormethane extracts of A. betulina and A. crenulata and an aqueous extract of A. betulina showed a Trolox equivalent antioxidant capacity (TEAC) of 11.8 µM Trolox. Recent in vitro studies with a commercial aqueous extract of buchu revealed increased uptake of glucose added to 3T3-L1 cell line, significant inhibition of the respiratory burst of neutrophils and monocytes, reduction in the expression of adhesion molecules and inhibition of the release of IL-6 and TNF-α. In diabetic rats the ingestion of aqueous buchu extract completely normalized the glucose level and in rats receiving a high fat diet the consumption of aqueous buchu extract resulted in less weight gain and less intraperitoneal fat gain as well as reduction of elevated blood pressure to normal associated with cardioprotective effects. Limitations in the hitherto conducted research lie in the undisclosed composition of the buchu extracts used and the difficulty in extrapolating data from animal studies to humans. Health claims for buchu products need to be substantiated by randomized, double-blind and placebo-controlled studies. Only then can they be promoted for their true therapeutic potential.

From Bush Medicine to Modern Phytopharmaceutical: A Bibliographic Review of Devil's Claw (Harpagophytum spp.).

Devil's claw (Harpagophytum spp., Pedaliaceae) is one of the best-documented phytomedicines. Its mode of action is largely elucidated, and its efficacy and excellent safety profile have been demonstrated in a long list of clinical investigations. The author conducted a bibliographic review which not only included peer-reviewed papers published in scientific journals but also a vast amount of grey literature, such as theses and reports initiated by governmental as well as non-governmental organizations, thus allowing for a more holistic presentation of the available evidence. Close to 700 sources published over the course of two centuries were identified, confirmed, and cataloged. The purpose of the review is three-fold: to trace the historical milestones in devil's claw becoming a modern herbal medicine, to point out gaps in the seemingly all-encompassing body of research, and to provide the reader with a reliable and comprehensive bibliography. The review covers aspects of ethnobotany, taxonomy, history of product development and commercialization, chemistry, pharmacology, toxicology, as well as clinical efficacy and safety. It is concluded that three areas stand out in need of further investigation. The taxonomical assessment of the genus is outdated and lacking. A revision is needed to account for intra- and inter-specific, geographical, and chemo-taxonomical variation, including variation in composition. Further research is needed to conclusively elucidate the active compound(s). Confounded by early substitution, intermixture, and blending, it has yet to be demonstrated beyond a reasonable doubt that both (or all) Harpagophytum spp. are equally (and interchangeably) safe and efficacious in clinical practice.

Sceletium for Managing Anxiety, Depression and Cognitive Impairment: A Traditional Herbal Medicine in Modern-Day Regulatory Systems.

Modern-day regulatory systems governing conditions for how health products enter national markets constitute a barrier of access for traditional herbal medicines on an international level. Regulatory intentions are focused on ensuring that consumers are being provided with safe, efficacious and high-quality products that, however, collaterally limit opportunities for traditional herbal medicinal products, especially those that do not already have a long-standing tradition of use established in the respective national marketplaces. This case study investigates and compares how a Southern African herbal medicine with great potential as an anxiolytic and mild antidepressant - Mesembryanthemum tortuosum L. [syn. Sceletium tortuosum (L.) N.E.Br.] aerial parts - fares internationally in today's regulatory environments. It is argued that inadvertent regulatory favoritism combined with the lack of means for adequate protection of intellectual property may obstruct innovation by creating an almost insurmountable economical hurdle for successful product development and introduction of botanicals from developing countries into most of the world's health product markets.

Botanical drugs and supplements affecting the immune response in the time of COVID-19: Implications for research and clinical practice.

In times of health crisis, including the current COVID-19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday self-care and health care, but, since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical, and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well-being. Newly emerging viral infections, specifically COVID-19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, especially regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and antiinflammatory effects include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate-yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections.

The Role of Adaptogens in Prophylaxis and Treatment of Viral Respiratory Infections.

The aim of our review is to demonstrate the potential of herbal preparations, specifically adaptogens for prevention and treatment of respiratory infections, as well as convalescence, specifically through supporting a challenged immune system, increasing resistance to viral infection, inhibiting severe inflammatory progression, and driving effective recovery. The evidence from pre-clinical and clinical studies with Andrographis paniculata, Eleutherococcus senticosus, Glycyrrhiza spp., Panax spp., Rhodiola rosea, Schisandra chinensis, Withania somnifera, their combination products and melatonin suggests that adaptogens can be useful in prophylaxis and treatment of viral infections at all stages of progression of inflammation as well as in aiding recovery of the organism by (i) modulating innate and adaptive immunity, (ii) anti-inflammatory activity, (iii) detoxification and repair of oxidative stress-induced damage in compromised cells, (iv) direct antiviral effects of inhibiting viral docking or replication, and (v) improving quality of life during convalescence.

Astaxanthin: How much is too much? A safety review.

Astaxanthin (AX)-containing preparations are increasingly popular as health food supplements. Evaluating the maximum safe daily intake of AX is important when setting dose levels for these products and currently, there are discrepancies in recommendations by different regulatory authorities. We have therefore conducted a review of approved dose levels, clinical trials of natural AX, and toxicological studies with natural and synthetic AX. Recommended or approved doses varied in different countries and ranged between 2 and 24 mg. We reviewed 87 human studies, none of which found safety concerns with natural AX supplementation, 35 with doses ≥12 mg/day. An acceptable daily intake (ADI) of 2 mg as recently proposed by European Food Safety Authority was based on a toxicological study in rats using synthetic AX. However, synthetically produced AX is chemically different from natural AX, so results with synthetic AX should not be used in assessing natural AX safety. In addition, few safety studies have been conducted in either humans or animals with synthetic AX. We therefore recommend the ADI for natural AX to be based only on studies conducted with natural AX and further studies to be conducted with synthetic AX (including human clinical trials) to establish a separate ADI for synthetic AX.

Phytochemical Analysis and Anti-Inflammatory Activity of the Extracts of the African Medicinal Plant Ximenia caffra.

A method was developed for identification and quantification of polyphenols in the leaves of Ximenia caffra using HPLC/UV/MS. Based on analyzing the MS and UV data and in comparison to the authentic standards, a total of 10 polyphenols were identified and quantified, including gallic acid, catechin, quercetin, kaempferol, and their derivatives. The total content of these compounds was found to be approximately 19.45 mg/g in the leaf and the most abundant is quercetin-rutinoside (9.08 mg/g). The total phenolic content as measured by Folin-Ciocalteu assay was 261.87 ± 7.11 mg GAE/g and the total antioxidant capacity as measured in vitro was 1.46 ± 0.01 mmol Trolox/g. The antiproliferative effect of the leaf extract was measured by MTS assay with IC50 value of 239.0 ± 44.5 µg/mL. Cell-based assays show that the leaf extract inhibits the mRNA expression of proinflammatory genes (IL-6, iNOS, and TNF-α) by using RT-qPCR, implying its anti-inflammatory effects. It was further demonstrated that the underlying therapeutic mechanism involves the suppression of NF-κB, a shared pathway between cell death and inflammation.

Devil's Claw (Harpagophytum procumbens DC): an evidence-based systematic review by the Natural Standard Research Collaboration.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interaction, adverse effects, toxicology, and dosing.

Lemon balm (Melissa officinalis L.): an evidence-based systematic review by the Natural Standard Research Collaboration.

An evidence-based systematic review including written and statistical analysis of scientific analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetic/dynamics, interactions, adverse effect, toxicology, and dosing.