METHODOLOGICAL APPROACHES TO STANDARDIZATION OF COMPLEX PHYTOADAPTOGENS FOR PREVENTIVE ONCOLOGY

Asian and Siberian ginseng as a potential modulator of immune function: an in vitro cytokine study using mouse macrophages

Although new antidiabetic agents are introduced, alternative medicine with natural compounds such as ginseng offer a potential benefit, as they have a wide margin of safety with no no side-effects. Following informed consent patients with type 2 diabetes (oral medication 80%, insulin therapy 20%) were randomly assigned to receive an extract of Siberian (480 mg/day; n = 27) American (Panax) ginseng (480 mg/day; n = 27), or a placebo preparation over a period of three months. Patients and physician were blinded as to the kind of ginseng being administered. Fasting (BZfast) and postprandial blood glucose level (BZpp), HbA1c, total cholesterol (TC) and triglyceride (TG) levels were determined each week and at the end of each month. In addition, the degree of peripheral neuropathy was evaluated by an electrical stimulus at 5 Hz determining threshold levels for feeling of sensation and pain at both lower extremities at start and after each month of treatment. Contrary to placebo and Panax ginseng, Siberian ginseng intake resulted in a highly significant decline (p < 0.001) of fasting blood sugar, and postprandial blood sugar level at the end of the three-month period. Also, Siberian ginseng lowered significantly (p < 0.001) HbA1c, TC and TG levels after the 12-week period. Patients taking Siberian ginseng demonstrated some recovery of sensory to an electrical stimulus. Since eleutherosides are only found in Siberian ginseng, they seem to contribute to the observed therapeutic effect, which may be due to their ability to blockade of P-glycoprotein, an ATP-dependent drug efflux pump, which is responsible for an increase in insulin resistance. Since Siberian ginseng induced no adverse side effects, its additional intake is able to fine-tune the pathological glucose metabolism, also reducing symtoms of peripheral polyneuropathy.

25617 Topical formulation with an ingredient blend composed of Rhodiola rosea and Eleutherococcus senticosus (Siberian ginseng) induces stress protective response on human skin against intrinsic and extrinsic stressors

Differential antioxidant and quinone reductase inducing activity of American, Asian, and Siberian ginseng☆

Adaptogen-based plant formulations play an important role in traditional medicine and have been used in medical practice to increase the resistance of individuals. Rhodiola rosea (RR) and Panax ginseng (PG) exhibit adaptogenic properties and are related to the recovery of homeostasis and strengthen systems impaired by stress. This study aimed to evaluate the effects of RR and PG on metabolic profile and muscle damage parameters in Wistar rats submitted to swimming. Animals were divided according to the following: G1: control group; G2: group that was submitted to swimming; G3: group treated with PG; G4: group treated with PG and submitted to swimming; G5: treated with RR; and G6: treated with RR and submitted to swimming. At the end of the experimental protocol, groups G2, G4, and G6 practiced swimming for a period five times longer than during the previous 30 days. Anthropometric and biochemical parameters were investigated, and no significant results were found in the groups. Nevertheless, animals treated with PG and RR reduced the levels of creatine phosphokinase (CPK) and lactic dehydrogenase (LDH). Our findings demonstrate that both PG and RR produced a significant reduction in the levels of CPK and LDH after physical stress, suggesting that they can be used to improve physical performance. For these reasons, we may say that these plants may be used to minimize the stress promoted by the practice of physical exercises.

Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defence mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation.

The use of herbs or their parts: leaves, roots, rhizomes, flowers, seeds, natural strains, as well as extracts or isolated metabolites is becoming more and more popular. Natural remedies not only act prophylactically, but also help to alleviate symptoms of many diseases and enhance the overall functioning of the internal organs. Many raw materials of natural origin plays a role in treatment of health problems, and also in case of serious diseases such as depression. Depression (affective disorder) now affects about 10% of the population, but in next few years due to the development of civilization and increasing pace of life, the probable number of people suffering from this disease can grow rapidly. Natural raw materials such as Bacopa monnieri, Crocus sativus, Eleutherococcus senticosus, Griffonia simplicifolia, Hypericum perforatum, Sceletium tortuosum, Piper methysticum, Rhodiola rosea, Aspalathus linearis, Camellia sinensis, Ficus carica, Lycium chinense, Cuminum cyminum, Panax Ginseng can effectively assist the prevention and treatment of depression. Daily diet may also have positive effect in prevention of this disease. It was found that 5-hydroxy-L-tryptophan, L-tryptophan (which are precursors of serotonin in the CNS), omega-3 fatty acids and anthranilic acid (vitamin L1) are able to improve mood. L-Tryptophan, 5-hydroxy-L-tryptophan are present in the largest quantities in the fruiting bodies of edible mushrooms. Omega-3 fatty acids are found in the flesh of fish, walnuts, soybeans, beans and chicken egg protein, while the anthranilic acid is commonly found in plants.

The involvement of brain-derived neurotrophic factor (BDNF) in different central nervous system (CNS) diseases suggests that this neurotrophin may represent an interesting and reliable therapeutic target. Accordingly, the search for new compounds, also from natural sources, able to modulate BDNF has been increasingly explored. The present review considers the literature on the effects of botanicals on BDNF. Botanicals considered were Bacopa monnieri (L.) Pennell, Coffea arabica L., Crocus sativus L., Eleutherococcus senticosus Maxim., Camellia sinensis (L.) Kuntze (green tea), Ginkgo biloba L., Hypericum perforatum L., Olea europaea L. (olive oil), Panax ginseng C.A. Meyer, Rhodiola rosea L., Salvia miltiorrhiza Bunge, Vitis vinifera L., Withania somnifera (L.) Dunal, and Perilla frutescens (L.) Britton. The effect of the active principles responsible for the efficacy of the extracts is reviewed and discussed as well. The high number of articles published (more than one hundred manuscripts for 14 botanicals) supports the growing interest in the use of natural products as BDNF modulators. The studies reported strengthen the hypothesis that botanicals may be considered useful modulators of BDNF in CNS diseases, without high side effects. Further clinical studies are mandatory to confirm botanicals as preventive agents or as useful adjuvant to the pharmacological treatment.

Liver diseases, including hepatitis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis, pose significant global health challenges. Chronic liver damage is often exacerbated by oxidative stress, inflammation, immune dysregulation, and metabolic imbalances. Adaptogens are a class of natural substances known for their ability to enhance the body's resilience to physical, emotional, and environmental stressors. Historically used in Ayurveda, Traditional Chinese Medicine (TCM), and Russian medicine, adaptogens such as Withania somnifera (Ashwagandha), Rhodiola rosea, Schisandra chinensis, Panax ginseng, and Eleutherococcus senticosus have demonstrated hepatoprotective, antioxidant, and anti-inflammatory properties. This chapter explores the pathophysiological mechanisms of liver disease and how adaptogens modulate stress pathways, regulate inflammation, and enhance hepatic detoxification processes. It also discusses emerging research on adaptogenic formulations, their potential synergistic effects, and challenges related to standardization and clinical validation. Integrating adaptogens into conventional liver disease management may offer a holistic and complementary approach, supporting liver function, metabolic balance, and overall well-being.

People are constantly exposed to adverse environmental factors that affect their health. If combined with hereditary predisposition, they may lead to gerontological changes that reduce healthy and working life expectancy. Some measures can prevent premature aging, e.g., a balanced diet or biologically active anti-aging substances also called geroprotectors. This article reviews biologically active geroprotectors with a view to select promising components for novel biologically active additives and functional foods. The review covered five years of Russian research articles and patents on biologically active anti-aging agents indexed in the National Center for Biotechnology Information, ScienceDirect, eLIBRARY.RU, and the database of the Federal Institute of Industrial Property. The domestic market demonstrates a growing demand for biologically active supplements: in 2023, it increased by 10% in value terms as consumers’ interest in a healthy and long life continues to grow. The review also included quality criteria for biologically active anti-ageing agents, e.g., such plant metabolites as vitamins, polyphenols, antioxidants, adaptogens, peptides, etc. Thymalin, epithalamin, dasatinib, and epithalon are available on the domestic market. The list of potential anti-aging agents includes ethylamine, carnosine, glutathione, ubiquinone, curcumin, rutin, quercetin, resveratrol, senolytics, and sirutins. These biologically active substances prevent oxidative stress, accumulation of lipofuscin, and senescent cells. The most effective anti-aging agents come from Vitis amurensis, Rhodiola rosea, Schisandra chinensis, Galega officinalis, Eleutherococcus senticosus, Withania somnifera, and Panax ginseng.

Classic phytoadaptogens (Panax ginseng, Rhodiola rosea, Aralia mandshurica, Oplopanax elatus, Eleutherococcus senticosus, Leuzea carthamoides, Schisandra chinensis) have a complex protective effects, increasing the antitumor control of organisms. However, resistance to some adaptogens can develop. Therefore, the elaboration of multicomponent phytoadaptogen complexes based on the principle of a rational combination of complementary biologically active substances are relevant and scientifically significant. The use of several adaptogens in the herbal formula considers the absence of the organisms resistance. The review presents Russian and foreign studies devoted to the search for potential phytoadaptogens, as well as the development of complexes based on them. The possibility of regulating the protective systems of organism by components of phytoextracts with different points of pharmacological action has been shown. The advantages of multicomponent phytomixtures in comparison with individual adaptogens are substantiated. The many-sided experimental in vitro and in vivo investigations of Russian herbal formula are colligated. Its clinical application has been demonstrated in relation to a benign tumour, precancerous disease, advanced cancer process, and neurodegenerative pathology. The prospects of using the herbal formula preparations as a part of integrative medicine including oncological and age-related pathologies are shown.

Plant-based nootropics are a diverse group of natural drugs that can improve cognitive abilities through various physiological mechanisms, especially in cases where these functions are weakened or impaired. In many cases, the nootropics enhance erythrocyte plasticity and inhibit aggregation, which improves the blood’s rheological properties and increases its flow to the brain. Many of these formulations possess antioxidant activity that protects brain tissue from neurotoxicity and improves the brain’s oxygen supply. They can induce the synthesis of neuronal proteins, nucleic acids, and phospholipids for constructing and repairing neurohormonal membranes. These natural compounds can potentially be present in a great variety of herbs, shrubs, and even some trees and vines. The plant species reviewed here were selected based on the availability of verifiable experimental data and clinical trials investigating potential nootropic effects. Original research articles, relevant animal studies, meta-analyses, systematic reviews, and clinical trials were included in this review. Selected representatives of this heterogeneous group included Bacopa monnieri (L.) Wettst., Centella asiatica (L.) Urban, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., Ginkgo biloba L., Lepidium meyenii Walp., Panax ginseng C.A. Meyer, Paullinia cupana Kunth, Rhodiola rosea L., Schisandra chinensis (Turcz.) Baill., and Withania somnifera (L.) Dunal. The species are depicted and described, together with their active components and nootropic effects, and evidence of their efficacy is presented. The study provides brief descriptions of the representative species, their occurrence, history, and the chemical composition of the principle medicinal compounds, with uses, indications, experimental treatments, dosages, possible side effects, and contraindications. Most plant nootropics must be taken at optimal doses for extended periods before measurable improvement occurs, but they are generally very well tolerated. Their psychoactive properties are not produced by a single molecule but by a synergistic combination of several compounds. The available data suggest that including extracts from these plants in medicinal products to treat cognitive disorders can have substantial potential therapeutic benefits.

Adaptogens are synthetic compounds (bromantane, levamisole, aphobazole, bemethyl, etc.) or plant extracts that have the ability to enhance the body’s stability against physical loads without increasing oxygen consumption. Extracts from Panax ginseng, Eleutherococcus senticosus, Rhaponticum carthamoides, Rhodiola rosea, and Schisandra chinensis are considered to be naturally occurring adaptogens and, in particular, plant adaptogens. The aim of this study is to evaluate the use of plant adaptogens in the past and now, as well as to outline the prospects of their future applications. The use of natural adaptogens by humans has a rich history—they are used in recovery from illness, physical weakness, memory impairment, and other conditions. About 50 years ago, plant adaptogens were first used in professional sports due to their high potential to increase the body’s resistance to stress and to improve physical endurance. Although now many people take plant adaptogens, the clinical trials on human are limited. The data from the meta-analysis showed that plant adaptogens could provide a number of benefits in the treatment of chronic fatigue, cognitive impairment, and immune protection. In the future, there is great potential to register medicinal products that contain plant adaptogens for therapeutic purposes.

Introduction The hypothalamic–pituitary–adrenal (HPA) axis plays a central role in the stress response. Plants, herbs, spices, and plant-based nutrients may influence HPA-axis activity. Objective To evaluate randomised controlled, human trials assessing the effects of single plants or phytonutrients on HPA-axis related hormones. Methods A systematic review of PubMed, Cochrane library, and the Cumulative Index to Nursing and Allied Health Literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria comprised of human, randomised controlled studies with a control intervention examining the effects of a single herb, spice, plant, or extract on pre- and post-changes in blood, saliva, urine, or hair concentrations of cortisol, cortisone, corticotrophin-releasing hormone, or adrenocorticotropic hormone. Databases were searched from inception until October 2020. Results Fifty-two studies were identified examining the effects of ashwagandha, Korean ginseng, St John's Wort, cannabidiol, Rhodiola rosea, curcumin, cherry juice, asparagus, Jiaogulan, Black cohosh, Siberian ginseng, Bacopa monnieri, blueberries, green tea, Caralluma fimbriata, cashew apple juice, melon, American ginseng, Ginkgo biloba, grape juice, grapefruit juice, rosella, hops, mangosteen, holy basil, and pomegranate juice. Due to significant variability in study designs, the effect of phytonutrients on HPA-axis activity in humans was unclear. The most consistent finding was a morning, cortisol-lowering effect from ashwagandha supplementation. Conclusion For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear. Before more definitive conclusions about the effects of phytonutrients on the HPA-axis can be made, further research is required.

Background: In the 1960s, research into plant adaptogens began. Plants with adaptogenic properties have rich phytochemical compositions and have been used by humanity since ancient times. However, it is not still clear whether the adaptogenic properties are because of specific compounds or because of the whole plant extracts. The aim of this review is to compare the bioactive compounds in the different parts of these plants. Methods: The search strategy was based on studies related to the isolation of bioactive compounds from Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus, and Panax ginseng. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Results: This review includes data from 259 articles. The phytochemicals isolated from Rhaponticum carthamoides, Lepidium meyenii, Eleutherococcus senticosus, and Panax ginseng were described and classified in several categories. Conclusions: Plant species have always played an important role in drug discovery because their effectiveness is based on the hundreds of years of experience with folk medicine in different nations. In our view, there is great potential in the near future for some of the phytochemicals found in these plants species to become pharmaceutical agents.