Withania somnifera (L.) Dunal, popularly known as Ashwagandha or Indian ginseng, is well acclaimed for its health-enhancing effects, including its potent immunomodulatory, anti-inflammatory, neuroprotective, and anti-tumorigenic properties. The prime biological effectors of these attributes are a diverse group of ergostane-based steroidal lactones termed withanolides. Withanones and withanosides are distributed differentially across the plant body, whereas withanolides and withanones are known to be more abundant in leaves, while withanosides are found exclusively in the roots of the plants. Standardized W. somnifera extract is Generally Recognized as Safe (GRAS)-affirmed, however, moderate to severe toxic manifestations may occur at high dosages. Withaferin A, which also happens to be the primary bioactive ingredient for the effectiveness of this plant. There have been contrasting reports regarding the distribution of withaferin A in W. somnifera. While most reports state that the roots of the plant have the highest concentrations of this phytochemical, several others have indicated that leaves can accumulate withaferin A in proportionately higher amounts. A comprehensive survey of the available reports suggests that the biological effects of Ashwagandha are grossly synergistic in nature, with many withanolides together mediating the desired physiological effect. In addition, an assorted formulation of withanolides can also neutralize the toxic effects (if any) associated with withaferin A. This mini-review presents a fresh take on the recent developments regarding the safety and toxicity of the plant, along with a critical assessment of the use of roots against leaves as well as whole plants to develop therapeutic formulations. Going by the currently available scientific evidence, it is safe to infer that the use of whole plant formulations instead of exclusively root or leaf recipes may present the best possible option for further exploration of therapeutic benefits from this novel medicinal plant. Highlights Therapeutic potential of withanolides owes to the presence of α,β unsaturated ketone which binds to amines, alcohols, and esters and 5β, 6β epoxy group which react with side chain thiols of proteins. At concentrations above NOAEL (no observed adverse effect level), the same mechanisms contribute towards toxicity of the molecule. Although withanosides are found exclusively in roots, whole plants have higher contents of withanones and withanolides. Whole plant-based formulations have other metabolites which can nullify the toxicity associated with roots. Extracts made from whole plants, therefore can holistically impart all therapeutic benefits as well as mitigate toxicity.

Background Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. Objective The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. Results Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. Conclusion The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

Ethnopharmacological relevanceThe use of herbal tea infusions is widespread in ethnomedicine throughout the world. One such ethnobotanical is kratom (Mitragyna speciosa Korth., Rubiaceae) which has gained considerable interest as an herbal supplement in recent years in the West beyond its native Southeast Asia. Traditional, kratom leaves are either chewed fresh or made into a tea infusion to treat fatigue, pain, or diarrhea. However, dried kratom leaf powder and hydroalcoholic extracts are more commonly used in Western countries, raising the question of exposure to kratom alkaloids and related effects. Aim of the studyA specific kratom tea bag product was analyzed for mitragynine content using tea infusion preparation and methanolic extraction. Consumers of both the tea bag product and other kratom products completed an online anonymous survey to determine demographics, kratom use patterns, and self-reported beneficial and detrimental effects. Materials and methodsKratom tea bag samples were extracted using pH-adjusted water or methanol and analyzed using an established LC-QTOF method. A modified kratom survey was distributed to consumers of the kratom tea bag products and other kratom products over a 14-month period. ResultsTea infusion extraction of tea bag samples resulted in lower mitragynine levels (0.062–0.131% (w/w)) compared to methanolic extraction (0.485–0.616% (w/w)). Kratom tea bag consumers did report similar, although often milder beneficial effects compared to consumers using other kratom products. Overall self-reported health was better among kratom tea bag consumers whereas improvement of a diagnosed medical condition was less in tea bag consumers compared to those using other kratom products. ConclusionsTraditional tea infusions of Mitragyna speciosa dried leaves provide benefits to consumers despite substantially lower mitragynine content. These effects may be less pronounced but indicate that tea infusions provide a potentially safer formulation compared to more concentrated products.

The prevalence of obesity has increased unprecedentedly from 30.5% to 42.4% over the last two decades. Indigenous knowledge and scientific explorations have led to the development of quite a few phytochemicals as dietary supplements for its effective management. However, most of them have been rendered ineffective for long-term weight management due to poor bioavailability. Several studies have also indicated the need for regular exercise to complement the action of these bioactives. However, in spite of all meaningful endeavours for assuring effective body recomposition, the trajectory of obesity had never declined. This chapter provides a fresh update of the prevailing weight loss myths and misconceptions which have thwarted the effective management of obesity. Additionally, a novel stimulant and sugar free bioencapsulated formulation of phytoceuticals is discussed which has the potential to curb obesity and ensure a holistic solution for the well-being of the body.

Abstract Turmeric's main ingredient, curcumin (diferuloylmethane), is a polyphenol obtained from the Curcuma longa plant. Since curcumin is nontoxic and has a wide range of medicinal qualities, including antioxidant, analgesic, anti-inflammatory, and antibacterial action, it has been widely employed in Ayurvedic medicine for ages. Curcumin has recently been discovered to have anti-cancer properties through its impact on numerous biological pathways that are involved in carcinogenesis, metastasis, tumorigenesis, cell cycle regulation, mutagenesis, and oncogene expression. In this study, we determined the antiproliferative activity and apoptosis-inducing mechanism of C. longa (Turmimax®) on human cancer cells. The cytotoxic effect was evaluated against HeLa cell lines using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. A flow cytometric analysis was performed to detect apoptotic cell death. Turmimax® exhibits promising properties as a potential anti-cancer therapeutic agent in human cervical adenocarcinomas and possibly other cancer types, with an IC50 value of 87.89µg/mL. In HeLa cells treated with Turmimax®, cell cycle arrest was seen at the G0/G1 and S phases. By inducing apoptosis and increasing the number of apoptotic cells in a dose-dependent manner, the experimental data suggest that Turmimax® has considerable promise in the prevention and treatment of cancer.

Current agricultural practices, food processing, and extensive availability of unhealthy “fast foods” impose a broad spectrum of degenerative disorders including bacterial, viral, parasitic, fungal, and yeast infections, all of which became a leading cause of death. An infection is defined as “The invasion and growth of germs in the body.” Several of these germs are opportunistic anaerobic organisms, while their propagation and proliferation potentiate the anaerobic bio-environment alarmingly. An ideal therapeutic objective is to restore a healthier cellular “aerobic” metabolic environment. This chapter will extensively focus on three important infectious disorders (i) COVID-19 infection, (ii) Herpesvirus infection, and (iii) Candida albicans yeast infections. Disease etiology, mechanisms, and pathology will be extensively discussed. Prevention and the potential of therapeutic interventions by structurally diverse nutraceuticals, phytopharmaceuticals, probiotics, and micronutrients will be extensively reviewed.

Noncoding RNAs (ncRNAs) are a class of RNA molecules that are not translated into protein Historically, ncRNA were believed to simply be by-products of transcription with little effect on a cell; however, advances in genetic sequencing technology have opened up a new world of ncRNA and their roles in cellular and molecular processes. Two major categories of ncRNAs have emerged housekeeping ncRNAs and regulatory ncRNAs. Housekeeping ncRNAs are found throughout a cell and are primarily involved in the regulation of basic cell functions.Regulatory ncRNAs are focused on the oversight of gene expression at each level of transcription. Housekeeping ncRNAs generally range from 50 to 500 nucleotides (nt) in length and can be further divided into five categoriestRNAs, rRNAs, telomerase RNAs, small nuclear RNAs (snRNAs), and small nucleolar RNAs (snoRNAs). Regulatory ncRNAs are a much larger group and require more in-depth categorization, generally based on the average size. Transcripts smaller than 200nt, the small noncoding RNAs, and transcripts that are larger than 200nt the long noncoding RNAs (lncRNAs). With the development of more powerful sequencing techniques, we have been able to take first steps into illuminating the role that ncRNAs play in bacterial infection. We have learned that bacteria are able to release vesicles that contain packages of ncRNA that can fuse with host cells. These ncRNA packages are then able to lower the hosts immune response. More research is needed in this field to fully understand the importance of ncRNAs.

Introduction Polycystic Ovary Syndrome (PCOS) is an endocrine disorder which accounts for infertility around the world. The disease is characterized by elevated secretion of androgens in the women which results in enlargement of ovaries with accumulation of fluid filled cysts, irregular menstrual cycles, and hirsutism. This study reports the efficacy of a patented, standardized Trigonella foenum-graecum extract (Furocyst®) as an effective phytotherapeutic for effective management of PCOS. Objective This randomized one-arm study assessed the efficacy of Furocyst® in 107 female volunteers over a period of 12 consecutive weeks. Method Following approvals of the Institutional Ethical Committee and clinicaltrials.gov, 107 female volunteers (age: 18-45 years) were recruited. Subjects consumed Furocyst® capsules (1,000 mg/day p.o.) over a period of 12 consecutive weeks. Physical (Sonographic scan, Hirsutism Score, Menstrual cycle, Body Weight, BMI, Height, Waist Circumference and Blood Pressure) and biochemical parameters (LH/FSH ratio, TSH, Prolactin, Fasting insulin, Fasting Glucose, triglyceride, cholesterol, HOMA Index, free and total testosterone, 2-hour GTT, DHEAS) were assessed at the beginning of the study as well as at intervals of 4 weeks till 12 weeks to determine the efficacy of Furocyst® on PCOS induced damage on reproductive and endocrine system. Results Furocyst® treatment induced >40% reduction of mean cyst sizes in both ovaries with corresponding reduction of in ovarian volumes. LH:FSH ratio was also significantly improved with corresponding reduction in total testosterone and prolactin levels. As a result of improvement in endocrine function, menstrual cycle became regular in the subjects. Furocyst® also reduced the severity of other associated ailments such as insulin resistance, dyslipidemia, and improved liver function significantly. Conclusions This study reinstated the efficacy of Furocyst® as a safe phytotherapeutic to reverse the effects of PCOS inflicted damage on the female reproductive system without any adverse events.

Pyrroloquinoline quinone (PQQ), a potent coenzyme antioxidant naturally occurring in foods, has been demonstrated to protect brain cells by enhancing the expression of nerve growth factors (NGF) and NGF receptors, and suppressing the fibril formation and aggression of amyloid β. We developed mnemoPQQ®, a novel PQQ disodium salt and assessed its safety in GLP compliant toxicity studies. Acute toxicity studies of mnemoPQQ® in Wistar rats revealed that its LD50 was 1825- and 1410 mg/kg body weight (bw) in male and female rats, respectively, whereas its acute dermal LD50 was >2000 mg/kg bw. mnemoPQQ® was found to be nonirritant to the skin of rabbit in an acute dermal irritation/corrosion study, and classified mnemoPQQ® as a nonirritant to the eye of rabbit in an acute eye irritation/corrosion study. Ames bacterial reverse mutation assay and in vitro Mammalian cell gene mutation test exhibited its non-mutagenic potential. In mammalian in vivo erythrocyte micronucleus test, mnemoPQQ® was classified as non-clastogenic and non-mutagenic. A 90-day sub-chronic toxicity study, conducted at and up to the highest daily dose of 600 mg/kg body weight, revealed no evidence of systemic toxicity. All rats survived the treatment without any significant abnormal clinical signs and alterations in hematology, clinical chemistry, neurological evaluation, thyroid functions, reproductive hormone levels, sperm evaluations, vaginal cytology, endocrine functions, organ weight and gross and microscopic pathology findings. No observed adverse effect level (NOAEL) of mnemoPQQ® was found to be greater than 600 mg/kg body weight. These studies affirm that mnemoPQQ® has broad spectrum safety for human consumption.

Introduction: Undenatured type II collagen, derived from chicken sternum cartilage, is a novel functional ingredient, which has been demonstrated to improve joint health, flexibility and mobility, and enhancing motor functions. Undenatured type II collagen has been commercially available as functional dietary supplement worldwide for many years. Research studies demonstrated its broad-spectrum safety and clinical efficacy. Undenatured type II collagen requires very small amount to exhibit clinical efficacy and hence can be easily consumed over a long period of time as compared to the other joint care functional ingredients such as glucosamine and chondroitin. Since undenatured type II collagen is effective in relatively small amount, its accurate measurement in various dosage forms such as tablets and capsules become crucial to provide consumers optimal cost and joint-health benefits. Objective: In the present study, we modified the previously used Enzyme-Linked Immunosorbent Assay (ELISA) method to determine the active constituents precisely and accurately in formulations to affirm broad spectrum safety and clinical efficacy. Methods: Improved precision ELISA methodology was utilized to determine the amount of undenatured type II collagen extracted from chicken sternum cartilage. A commercially available Chondrex Collagen Detection Kit was used to determine the number of epitope (antigenic determinant) sites on the three-dimensional tightly-folded structured collagen. Time and temperature were set at ≥16 h or preferably within the range of 16 h to 24 h and at room temperatureResults: The results obtained from this improved ELISA method strongly supported the accuracy and validity, which correlates very well with the results of our earlier clinical studies, revealing the efficacy of undenatured type II collagen concentrations used. Furthermore, the modified ELISA method, designed by our team, revealed consistent and reproducible results on the basis of counting the epitope sites in undenatured type II collagen (NEXT-II®) of commercial batchesConclusion: Using this precisely modified ELISA method gave 8% of undenatured type II collagen in NEXT-II®, resulting in 3.2 mg in 40.0 mg of NEXT-II®. It also confirmed that administration of 3.2 mg of undenatured type II collagen a day, both in open-label and randomized clinical trials, was safe and efficacious for joint pain, flexibility and mobility, and motor function. Keywords: Undenatured type II collagen, NEXT-II®, ELISA method, Pepsin