CLINICAL STUDIES ON THE FOLLOWING INGREDIENTS:
Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives
Telomere length, a marker of cellular aging, decreases with age and it has been associated with aging-related diseases. Environmental factors, including diet and lifestyle factors, affect the rate of telomere shortening which can be reversed by telomerase. Telomerase activation by natural molecules has been suggested to be an anti-aging modulator that can play a role in the treatment of aging-related diseases. This study aimed to investigate the effect of natural compounds on telomerase activity in human peripheral blood mononuclear cells (PBMCs). The tested compounds included Centella asiatica extract formulation (08AGTLF), Astragalus extract formulation (Nutrient 4), TA-65 (containing Astragalus membranaceus extract), oleanolic acid (OA), maslinic acid (MA), and 3 multi-nutrient formulas (Nutrients 1, 2 and 3) at various concentrations. The mean absorbance values of telomerase activity measured following treatment with some of the above-mentioned formulations were statistically significantly higher compared to those of the untreated cells. In particular, in order of importance with respect to telomerase activation from highest to lowest, 08AGTLF, OA, Nutrient 4, TA-65, MA, Nutrient 3 and Nutrient 2, triggered statistically significant increase in telomerase activity compared to the untreated cells. 08AGTLF reached the highest levels of telomerase activity reported to date, at least to our knowledge, increasing telomerase activity by 8.8 folds compared to untreated cells, while Nutrient 4 and OA were also potent activators (4.3-fold and 5.9-fold increase, respectively). On the whole, this study indicates that the synergistic effect of nutrients and natural compounds can activate telomerase and produce more potent formulations. Human clinical studies using these formulations are required to evaluate their mode of action. This would reveal the health benefits of telomerase activation through natural molecules and would shed new light onto the treatment of aging-related diseases.
Source: Tsoukalas, D., Fragkiadaki, P., Docea, A. O., Alegakis, A. K., Sarandi, E., Thanasoula, M., Spandidos, D. A., Tsatsakis, A., Razgonova, M. P., & Calina, D. “Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives.” Molecular medicine reports (2019), 20(4), 3701–3708.
Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic
Owing to a dramatic increase in average life expectancy and the Family Planning program of the 1970s - 1990s, China is rapidly becoming an aging society. Therefore, the investigation of healthspan-extending drugs becomes more urgent. Astragalus membranaceus (Huangqi) is a major medicinal herb that has been commonly used in many herbal formulations in the practice of traditional Chinese medicine (TCM) to treat a wide variety of diseases and body disorders, or marketed as life-prolonging extracts for human use in China, for more than 2000 years. The major components of Astragalus membranaceus are polysaccharides, flavonoids, and saponins. Pharmacological research indicates that the extract component of Astragalus membranaceus can increase telomerase activity, and has antioxidant, anti-inflammatory, immunoregulatory, anticancer, hypolipidemic, antihyperglycemic, hepatoprotective, expectorant, and diuretic effects. A proprietary extract of the dried root of Astragalus membranaceus, called TA-65, was associated with a significant age-reversal effect in the immune system. Our review focuses on the function and the underlying mechanisms of Astragalus membranaceus in lifespan extension, anti-vascular aging, anti-brain aging, and anti-cancer effects, based on experimental and clinical studies.
Source: Liu, P., Zhao, H., & Luo, Y. “Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic.” Aging and disease (2017), 8(6), 868–886.
Telomerase-Based Pharmacologic Enhancement of Antiviral Function of Human CD8+ T Lymphocytes
Telomerase reverse transcribes telomere DNA onto the ends of linear chromosomes and retards cellular aging. In contrast to most normal somatic cells, which show little or no telomerase activity, immune cells up-regulate telomerase in concert with activation. Nevertheless, during aging and chronic HIV-1 infection, there are high proportions of dysfunctional CD8+ CTL with short telomeres, suggesting that telomerase is limiting. The present study shows that exposure of CD8+ T lymphocytes from HIV-infected human donors to a small molecule telomerase activator (TAT2) modestly retards telomere shortening, increases proliferative potential, and, importantly, enhances cytokine/chemokine production and antiviral activity. The enhanced antiviral effects were abrogated in the presence of a potent and specific telomerase inhibitor, suggesting that TAT2 acts primarily through telomerase activation. Our study is the first to use a pharmacological telomerase-based approach to enhance immune function, thus directly addressing the telomere loss immunopathologic facet of chronic viral infection.
Telomeres, the TTAGGG tandem repeats at chromosome ends, become progressively shorter in dividing somatic cells (1). Numerous studies have shown associations between leukocyte telomere shortening and risk of disease, suggesting that these cells may serve as biomarkers for the cumulative burden of inflammation, chronic immune activation, or oxidative stress. Indeed, hypertension and increased insulin resistance are associated with shorter leukocyte telomere length in the participants of the Framingham heart study (2), and telomere shortening in peripheral blood leukocytes chronicles ischemic heart disease risk in older people (3). Leukocyte telomere length also correlates with bone mineral density, and shorter telomeres are seen in women with osteoporosis (4). Finally, in both aging and chronic HIV-1 infection, there are increased proportions of CD8+ T lymphocytes with shortened telomeres, reduced proliferative capacity and altered effector function (5). Thus, strategies to retard or prevent telomere loss may lead to novel treatments for a variety of human pathologies.
T and B lymphocytes transiently up-regulate telomerase, the cellular reverse transcriptase that adds telomeric DNA to the ends of chromosomes (6, 7, 8). Such telomerase activity is believed to mitigate the losses of replicative capacity and function caused by chronic antigenic stimulation, oxidative stress, and cellular aging (9, 10). However, the ability of CD8+ T lymphocytes to up-regulate telomerase is lost after repeated encounters with Ag, and continued chronic stimulation ultimately leads to critically short telomeres and other changes associated with replicative senescence (10, 11).
We hypothesized that sustained telomerase activity in chronically activated CD8+ T lymphocytes might prevent or delay immune dysfunction associated with aging and/or chronic disease. In previous studies, we showed that gene transduction of CD8+ T lymphocytes from HIV-1-infected persons with the human telomerase catalytic component (hTERT)4 (12) leads to preservation of antiviral functions, telomere length stabilization, and augmented proliferative potential (13). Whereas gene therapy has a number of drawbacks, such as inability to control gene expression and the potential side-effects of gene transduction, these proof-of-principle studies suggest that telomerase activation by nongenetic strategies may be an effective approach for enhancing immune function in certain chronic diseases.
In an empirical screen of traditional Chinese medicine plant extracts and compounds with reported properties of health maintenance and enhancement of immune function, we identified TAT2 (cycloastragenol) based on its ability to up-regulate the low, basal level of telomerase in neonatal human keratinocytes (unpublished data). We sought to determine whether TAT2 could increase telomerase activity in cells of the immune system, which exhibit high levels of active telomerase after stimulation with mitogens, activatory Abs (10), or Ag (14). In this study, we demonstrate that TAT2 can transiently activate telomerase, slow telomere loss, increase replicative capacity, and, importantly, enhance immune function in CD8+ T lymphocytes from HIV-1-infected persons. These data suggest a possible novel immune-based strategy to complement current treatments, which are primarily directed at the virus. The potential benefit of telomerase enhancement is underscored by the recent clinical study showing that HIV-1-infected persons who are able to control the infection for long periods of time (nonprogressors) have significantly higher constitutive telomerase activity in HIV-1-specific CD8+ T cells compared with “fast progressors” (15).
Source: Steven Russell Fauce, Beth D. Jamieson, Allison C. Chin, Ronald T. Mitsuyasu, Stan T. Parish, Hwee L. Ng, Christina M. Ramirez Kitchen, Otto O. Yang, Calvin B. Harley, Rita B. Effros. “Telomerase-Based Pharmacologic Enhancement of Antiviral Function of Human CD8+ T Lymphocytes.” The Journal of Immunology (November 15, 2008), 181 (10) 7400-7406;
Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity
Aim: To investigate the immunomodulating activity of astragalosides, the active compounds from a traditional tonic herb Astragalus membranaceus Bge, and to explore the molecular mechanisms underlying the actions, focusing on CD45 protein tyrosine phosphatase (CD45 PTPase), which plays a critical role in T lymphocyte activation.
Methods: Primary splenocytes and T cells were prepared from mice. CD45 PTPase activity was assessed using a colorimetric assay. Cell proliferation was measured using a [3H]-thymidine incorporation assay. Cytokine proteins and mRNAs were examined with ELISA and RT-PCR, respectively. Activation markers, including CD25 and CD69, were analyzed using flow cytometry. Activation of LCK (Tyr505) was detected using Western blot analysis. Mice were injected with the immunosuppressant cyclophosphamide (CTX, 80 mg/kg), and administered astragaloside II (50 mg/kg).
Results: Astragaloside I, II, III, and IV concentration-dependently increased the CD45-mediated of pNPP/OMFP hydrolysis with the EC50 values ranged from 3.33 to 10.42 μg/mL. Astragaloside II (10 and 30 nmol/L) significantly enhanced the proliferation of primary splenocytes induced by ConA, alloantigen or anti-CD3. Astragaloside II (30 nmol/L) significantly increased IL-2 and IFN-γ secretion, upregulated the mRNA levels of IFN-γ and T-bet in primary splenocytes, and promoted CD25 and CD69 expression on primary CD4+ T cells upon TCR stimulation. Furthermore, astragaloside II (100 nmol/L) promoted CD45-mediated dephosphorylation of LCK (Tyr505) in primary T cells, which could be blocked by a specific CD45 PTPase inhibitor. In CTX-induced immunosuppressed mice, oral administration of astragaloside II restored the proliferation of splenic T cells and the production of IFN-γ and IL-2. However, astragaloside II had no apparent effects on B cell proliferation.
Conclusion: Astragaloside II enhances T cell activation by regulating the activity of CD45 PTPase, which may explain why Astragalus membranaceus Bge is used as a tonic herb in treating immunosuppressive diseases.
Source: Wan, C.P. et al. “Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity.” Acta Pharmacol Sin (2013). 34(4):522–30.
Effects of astragalus on cardiac function and serum tumor necrosis factor-alpha level in patients with chronic heart failure
Objective: To explore the effects of Astragalus on cardiac function and serum tumor necrosis factor-alpha (TNF-alpha) level in patients with chronic heart failure (CHF).
Methods: Forty-five patients of Xin-qi deficiency or Xin-yang deficiency types were assigned to the Chinese medicine (CM) group and the Western medicine (WM) group by a randomizing digital table. Standard treatment for correcting heart failure, including digoxin, diuretics, etc. was administered to both groups, but to the CM group oral medication of Astragalus granule was given additionally at the dosage of 2.25 g twice a day, the treatment for both was continued for two weeks. NYHA cardiac functional grading, serum TNF-alpha level, left ventricular ejection fraction (LVEF) and walk distance in 6 min (WD) were measured before and after treatment, and a correlation analysis was carried out.
Results: After therapy, the level of TNF-alpha in the two groups decreased (P < 0.05) and it was lower in the CM group [(54.77 +/- 9.34) microg/L] than in the WM group [(62.10 +/- 9.94) microg/L] (P < 0.05); LVEF in the two groups increased (P < 0.05) and it was higher in the CM group [(64.45 +/- 12.47)%] than that in the WM group [(56.03 +/- 13.33)%] (P < 0.05); both groups' WD increased (P < 0.05) and it was longer in the CM group [(446.97 +/- 68.82) m] than in the WM group [(345.40 +/- 63.62) m] (P < 0.05); the improvement of cardiac functional grading in the CM group was outstriper than the WM group (P < 0.05). The improvement in cardiac function was negatively correlated with TNF-alpha level.
Conclusion: Astragalus can alleviate the calcium overload-induced myocardial damage and improve both systolic and diastolic functions of heart in patients with CHF.
Source: Yang QY, Lu S, Sun HR. [Effects of astragalus on cardiac function and serum tumor necrosis factor-alpha level in patients with chronic heart failure]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2010 Jul;30(7):699-701.
Pain relieving and protective effects of Astragalus hydroalcoholic extract in rat arthritis models
Objectives: The evaluation of the pharmacological profile of the dried 50% hydroalcoholic extract (50%HA) of Astragali radix in two different animal models of articular damage resembling osteoarthritis and rheumatoid arthritis.
Methods: Sodium monoiodoacetate (MIA) or complete Freund's adjuvant (CFA) was intra‐articular injected (day 0) in the rat tibiotarsal joint to induce damages mimicking osteoarthritis or rheumatoid arthritis. Pain measurements (responses to non‐noxious and noxious stimuli, spontaneous pain, articular pain) were assessed on days 7 and 14. On day 14, the tibiotarsal joints were explanted in order to measure the diameter and to assess histological evaluations. Furthermore, the plasmatic concentrations of inflammatory and anti‐inflammatory cytokines were measured.
Key findings: A single administration of 50%HA (300 mg/kg per os) significantly reduced both MIA‐induced pain and CFA‐induced pain (78% and 96% pain relief, respectively). The repeated administration prevented the development of hypersensitivity on day 14. The haematoxylin/eosin staining revealed that 50% HA attenuated joint alterations in MIA‐injected rats, and furthermore, the joint inflammatory infiltrate was reduced in both models (by about 50%). In CFA‐treated rats, 50%HA lowered the plasmatic levels of the pro‐inflammatory cytokines interleukin‐1β and tumour necrosis factor‐α as well as the joint diameter.
Conclusions: The 50% hydroalcoholic extract of Astragali radix is a valuable candidate for the adjuvant treatment of articular diseases.
Source: Mario Maresca Laura Micheli Lorenzo Cinci Anna Rita Bilia Carla Ghelardini Lorenzo Di Cesare Mannelli. “Pain relieving and protective effects of Astragalus hydroalcoholic extract in rat arthritis models.” Journal of Pharmacy and Pharmacology (2017), 69 (12); 1858-1870.
Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B
Aim: To examine the effects of Astragalus polysaccharide (APS), a component of an aqueous extract of Astragalus membranaceus roots, on protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin-receptor (IR) signal transduction, and its potential role in the amelioration of insulin resistance.
Methods: Ten-week-old fat-fed streptozotocin (STZ)-treated rats, an animal model of type II diabetes mellitus (TIIDM), were treated with APS (400 mg/kg p.o.) for 5 weeks. Insulin sensitivity was identified by the insulin-tolerance test. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle and liver were performed by immunoprecipitation or Western blotting. PTP1B activity was measured by an assay kit.
Results: The diabetic rats responded to APS with a significant decrease in body weight, plasma glucose, and improved insulin sensitivity. The activity and expression of PTP1B were elevated in the skeletal muscle and liver of TIIDM rats. Thus the insulin signaling in target tissues was diminished. APS reduced both PTP1B protein level and activity in the muscle, but not in the liver of TIIDM rats. Insulin-induced tyrosine phosphorylation of the IR beta-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle, but not in the liver of APS-treated TIIDM rats. There was no change in the activity or expression of PTP1B in APS-treated normal rats, and blood insulin levels did not change in TIIDM rats after treatment with APS.
Conclusion: APS enables insulin-sensitizing and hypoglycemic activity at least in part by decreasing the elevated expression and activity of PTP1B in the skeletal muscles of TIIDM rats.
Source: Wu Y, Ou-Yang JP, Wu K, Wang Y, Zhou YF, Wen CY. Hypoglycemic effect of Astragalus polysaccharide and its effect on PTP1B. Acta Pharmacol Sin. 2005 Mar;26(3):345-52. doi: 10.1111/j.1745-7254.2005.00062.x.
CAT’S CLAW - UNCARIA TOMENTOSA
The Amazon rain forest plant Uncaria tomentosa (cat’s claw) and its specific proanthocyanidin constituents are potent inhibitors and reducers of both brain plaques and tangles
Brain aging and Alzheimer’s disease both demonstrate the accumulation of beta-amyloid protein containing “plaques” and tau protein containing “tangles” that contribute to accelerated memory loss and cognitive decline. In the present investigation we identified a specific plant extract and its constituents as a potential alternative natural solution for preventing and reducing both brain “plaques and tangles”. PTI-00703 cat’s claw (Uncaria tomentosa from a specific Peruvian source), a specific and natural plant extract from the Amazon rain forest, was identified as a potent inhibitor and reducer of both beta-amyloid fibrils (the main component of “plaques”) and tau protein paired helical filaments/fibrils (the main component of “tangles”). PTI-00703 cat’s claw demonstrated both the ability to prevent formation/aggregation and disaggregate preformed Aβ fibrils (1–42 and 1–40) and tau protein tangles/filaments. The disaggregation/dissolution of Aβ fibrils occurred nearly instantly when PTI-00703 cat’s claw and Aβ fibrils were mixed together as shown by a variety of methods including Thioflavin T fluorometry, Congo red staining, Thioflavin S fluorescence and electron microscopy. Sophisticated structural elucidation studies identified the major fractions and specific constituents within PTI-00703 cat’s claw responsible for both the observed “plaque” and “tangle” inhibitory and reducing activity. Specific proanthocyanidins (i.e. epicatechin dimers and variants thereof) are newly identified polyphenolic components within Uncaria tomentosa that possess both “plaque and tangle” reducing and inhibitory activity. One major identified specific polyphenol within PTI-00703 cat’s claw was epicatechin-4β-8-epicatechin (i.e. an epicatechin dimer known as proanthocyanidin B2) that markedly reduced brain plaque load and improved short-term memory in younger and older APP “plaque-producing” (TASD-41) transgenic mice (bearing London and Swedish mutations). Proanthocyanidin B2 was also a potent inhibitor of brain inflammation as shown by reduction in astrocytosis and gliosis in TASD-41 transgenic mice. Blood-brain-barrier studies in Sprague-Dawley rats and CD-1 mice indicated that the major components of PTI-00703 cat’s claw crossed the blood-brain-barrier and entered the brain parenchyma within 2 minutes of being in the blood. The discovery of a natural plant extract from the Amazon rain forest plant (i.e. Uncaria tomentosa or cat’s claw) as both a potent “plaque and tangle” inhibitor and disaggregator is postulated to represent a potential breakthrough for the natural treatment of both normal brain aging and Alzheimer’s disease.
Source: Snow, A.D., Castillo, G.M., Nguyen, B.P. et al. “The Amazon rain forest plant Uncaria tomentosa (cat’s claw) and its specific proanthocyanidin constituents are potent inhibitors and reducers of both brain plaques and tangles.” Sci Rep 9, 561 (2019).
Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways
Rhynchophylline (Rhy) is an alkaloid isolated from Uncaria which has long been recommended for the treatment of central nervous diseases. In our study, the neuroprotective effect of Rhy was investigated in a stroke model, namely permanent middle cerebral artery occlusion (pMCAO). Rats were injected intraperitoneally once daily for four consecutive days before surgery and then received one more injection after surgery. The protein and mRNA levels of p-Akt, p-mTOR, apoptosis-related proteins (p-BAD and cleaved caspase-3), TLR2/4/9, NF-κB, MyD88, BDNF and claudin-5 were examined. Following pMCAO, Rhy treatment not only ameliorated neurological deficits, infarct volume and brain edema, but also increased claudin-5 and BDNF expressions (p < 0.05). Moreover, Rhy could activate PI3K/Akt/mTOR signaling while inhibiting TLRs/NF-κB pathway. Wortmannin, a selective PI3K inhibitor, could abolish the neuroprotective effect of Rhy and reverse the increment in p-Akt, p-mTOR and p-BAD levels. In conclusion, we hypothesize that Rhy protected against ischemic damage, probably via regulating the Akt/mTOR pathway.
Source: Huang H, Zhong R, Xia Z, Song J, Feng L. “Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways.” Molecules. (2014 Jul 30);19(8):11196-210.
[Cat's Claw: an herb from the Peruvian Amazon]
AIDS: Uncaria tomentosa, also known as cat's claw, an herb from the highlands of the Peruvian Amazon, has been used by natives for hundreds of years to treat immunologic and digestive disorders. Research began in the 1970s to discover the benefits of this plant in relieving symptoms of cancers, arthritis, and other ailments. It has the ability to cleanse the digestive tract, aiding victims of Crohn's, colitis, gastritis and more. In a 1989 study by Klaus Keplinger, several alkaloid oxidants found in the plant's roots showed an ability to stimulate the immune system. The principal alkaloids are isopteropodine and rynchophyiline. Extracts of cat's claw mixed with AZT in an experimental drug, called Krallendom, were effective in reducing symptoms in AIDS patients in Austria. The plant has been useful in reducing secondary effects of radiation and chemotherapy in cancer victims as well.
Source: Steinberg PN. “Una de Gato: una hierba prodigiosa de la selva humeda Peruana [Cat's Claw: an herb from the Peruvian Amazon].” Sidahora (1995 Apr-May):35-6. Spanish
Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100
A human intervention study was carried out using male volunteers attending a General Practice Clinic in New York City involving comparison of individuals supplemented with 350 mg x 2 C-Med-100 daily dose for two months with untreated controls for their abilities to respond to a 23 valent pneumococcal vaccine. C-Med-100 is a novel nutraceutical extract from the South American plant Uncaria tomentosa or Cat's Claw which is known to possess immune enhancing and antiinflammatory properties in animals. There were no toxic side effects observed as judged by medical examination, clinical chemistry and blood cell analysis. However, statistically significant immune enhancement for the individuals on C-Med-100 supplement was observed by (i) an elevation in the lymphocyte/neutrophil ratios of peripheral blood and (ii) a reduced decay in the 12 serotype antibody titer responses to pneumococcal vaccination at 5 months.
Source: Lamm S, Sheng Y, Pero RW. “Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100.” Phytomedicine (2001 Jul);8(4):267-74.
Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: A randomized controlled trial [ISRCTN38432711]
Background: This study was designed to determine if a natural mineral supplement, sierrasil, alone and in combination with a cat's claw extract (Uncaria guianensis), vincaria, has therapeutic potential in mild to moderate osteoarthritis of the knee.
Methods: Patients (n = 107) with mild to moderate osteoarthritis of the knee were randomly assigned to one of 4 groups; high dose sierrasil (3 g/day), low dose sierrasil (2 g/day), low dose sierrasil (2 g/day) + cat's claw extract (100 mg/day) or placebo, administered for 8 weeks. Treatment was double blinded. Primary efficacy variables were WOMAC scores (A, B, C and total). Visual analog score (VAS) for pain, consumption of rescue medication (paracetamol), and tolerability were secondary variables. Safety measures included vital signs and laboratory-based assays.
Results: Ninety-one of the 107 patients successfully completed the protocol. All four groups showed improvement in WOMAC and VAS scores after 8 weeks (p < 0.001), in all 3 groups receiving sierrasil the magnitude of benefits were greater vs. placebo (WOMAC Total 38–43% vs. 27%) but this was not statistically significant. In reference to baseline values sierrasil treated groups had a considerably faster onset of benefits. Placebo-treated individuals failed to show significant benefits at 4 weeks (11% reduction in total WOMAC). In contrast, after 1 or 2 weeks of therapy all the sierrasil groups displayed significant reductions in WOMAC scores (p < 0.05) and at week 4 displayed a 38–43% improvement. VAS was significantly improved at 4 weeks in all groups (p < 0.001) but was significantly greater in all sierrasil groups compared to placebo (p < 0.05). Rescue medication use was 28-23% lower in the herbomineral combination and high dose sierrasil groups although not statistically different from placebo (P = 0.101 and P = 0.193, respectively). Tolerability was good for all groups, no serious adverse events were noted and safety parameters remained unchanged.
Conclusion: The natural mineral supplement, sierrasil alone and in combination with a cat's claw extract, improved joint health and function within 1–2 weeks of treatment but significant benefits over placebo were not sustained, possibly due to rescue medication masking. Sierrasil may offer an alternative therapy in subjects with joint pain and dysfunction.
Source: Miller, M. J., Mehta, K., Kunte, S., Raut, V., Gala, J., Dhumale, R., Shukla, A., Tupalli, H., Parikh, H., Bobrowski, P., & Chaudhary, J. “Early relief of osteoarthritis symptoms with a natural mineral supplement and a herbomineral combination: a randomized controlled trial [ISRCTN38432711].” Journal of inflammation (2005), 2, 11.
Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial
Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.
Source: Santos Araújo, M., Farias, I. L., Gutierres, J., Dalmora, S. L., Flores, N., Farias, J., de Cruz, I., Chiesa, J., Morsch, V. M., & Chitolina Schetinger, M. R. “Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial.” Evidence-based complementary and alternative medicine : eCAM, (2012), 676984.
A water soluble extract from Uncaria tomentosa (Cat's Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin
Cat's Claw (Uncaria tomentosa) water extracts, essentially free of oxindole alkaloids, have been shown to possess a broad spectrum of biological activity including DNA repair enhancement and antiinflammatory properties. These two biological mechanisms are key molecular targets to develop treatments that protect skin exposed to ultraviolet light from the sun. Because C-Med-100, a Cat's Claw water extract, is the only documented natural source of components that can up-regulate simultaneously both DNA repair and antiinflammation, its ability to modulate DNA repair in human skin organ cultures was undertaken. For this purpose skin cultures were treated with or without 5 mg/mL C-Med-100, irradiated with 0-100 mJ/cm2 UVB, and microscopically analysed for necrosis as well as the level of pyrimidine dimers using immunofluorescent TT-dimer antibody staining. The data clearly demonstrated that co-incubation with C-Med-100 reduced skin cell death from UV exposure, and this protection was accounted for by a concomitant increase in DNA repair. Based on these results, it was concluded that C-Med-100 was a natural plant extract worthy of further consideration as a sunscreen product.
Source: Mammone T, Akesson C, Gan D, Giampapa V, Pero RW. “A water soluble extract from Uncaria tomentosa (Cat's Claw) is a potent enhancer of DNA repair in primary organ cultures of human skin.” Phytother Res. (2006 Mar);20(3):178-83.
A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults
Context: Stress is a state of mental or emotional strain or tension, which can lead to underperformance and adverse clinical conditions. Adaptogens are herbs that help in combating stress. Ayurvedic classical texts, animal studies and clinical studies describe Ashwagandha as a safe and effective adaptogen.
Aims: The aim of the study was to evaluate the safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha roots in reducing stress and anxiety and in improving the general well-being of adults who were under stress.
Settings and design: Single center, prospective, double-blind, randomized, placebo-controlled trial.
Materials and methods: A total of 64 subjects with a history of chronic stress were enrolled into the study after performing relevant clinical examinations and laboratory tests. These included a measurement of serum cortisol, and assessing their scores on standard stress-assessment questionnaires. They were randomized to either the placebo control group or the study drug treatment group, and were asked to take one capsule twice a day for a period of 60 days. In the study drug treatment group, each capsule contained 300 mg of high-concentration full-spectrum extract from the root of the Ashwagandha plant. During the treatment period (on Day 15, Day 30 and Day 45), a follow-up telephone call was made to all subjects to check for treatment compliance and to note any adverse reactions. Final safety and efficacy assessments were done on Day 60.
Statistical analysis: t-test, Mann-Whitney test.
Results: The treatment group that was given the high-concentration full-spectrum Ashwagandha root extract exhibited a significant reduction (P<0.0001) in scores on all the stress-assessment scales on Day 60, relative to the placebo group. The serum cortisol levels were substantially reduced (P=0.0006) in the Ashwagandha group, relative to the placebo group. The adverse effects were mild in nature and were comparable in both the groups. No serious adverse events were reported.
Conclusion: The findings of this study suggest that a high-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life.
Source: Chandrasekhar K, Kapoor J, Anishetty S. “A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults.” Indian J Psychol Med. (2012);34(3):255-62.
A double-blind, placebo-controlled evaluation of the anxiolytic efficacy ff an ethanolic extract of withania somnifera
A double-blind, placebo-controlled study was conducted to evaluate the efficacy an ethanolic extract of Aswagandha (Withania somnifera), in patients with ICD-10 anxiety disorders. The sample comprised 39 subjects, of whom 20 received the drug and 19 received placebo. The two groups were sociodemographically and clinically similar at baseline. At 2 and 6 weeks follow-up, data from approximately 85% of patients in each group were available for analysis. Statistical trends favouring the drug were observed at both time points. At 6 weeks, significantly more patients met a priori response criteria in the drug group (88.2%) as compared with the placebo group (50%). The drug was well-tolerated and did not occasion more adverse effects than did placebo. It is concluded that this ethanolic extract of Withania somnifera has useful anxiolytic potential and merits further investigation.
Source: Andrade C, Aswath A, Chaturvedi SK, Srinivasa M, Raguram R. “A double-blind, placebo-controlled evaluation of the anxiolytic efficacy ff an ethanolic extract of withania somnifera.” Indian J Psychiatry. (2000 Jul);42(3):295-301.
Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract - A Double-Blind, Randomized, Placebo-Controlled Trial
Chronic stress has been associated with a number of illnesses, including obesity. Ashwagandha is a well-known adaptogen and known for reducing stress and anxiety in humans. The objective of this study was to evaluate the safety and efficacy of a standardized root extract of Ashwagandha through a double-blind, randomized, placebo-controlled trial. A total of 52 subjects under chronic stress received either Ashwagandha (300 mg) or placebo twice daily. Primary efficacy measures were Perceived Stress Scale and Food Cravings Questionnaire. Secondary efficacy measures were Oxford Happiness Questionnaire, Three-Factor Eating Questionnaire, serum cortisol, body weight, and body mass index. Each subject was assessed at the start and at 4 and 8 weeks. The treatment with Ashwagandha resulted in significant improvements in primary and secondary measures. Also, the extract was found to be safe and tolerable. The outcome of this study suggests that Ashwagandha root extract can be used for body weight management in adults under chronic stress.
Source: Choudhary, D., Bhattacharyya, S., & Joshi, K. “Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial.” Journal of evidence-based complementary & alternative medicine (2017), 22(1), 96–106.
Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study
Background: Many women experience sexual dysfunction where there are orgasm disorders and sexual difficulties. Ashwagandha (Withania somnifera) is a herb known to improve the body's physical and psychological condition.
Objective: The purpose of the study was to determine the efficacy and safety of a high-concentration ashwagandha root extract (HCARE) supplementation for improving sexual function in healthy females.
Methods: In this pilot study, 50 study subjects were randomized to either (i) HCARE-treated group or (ii) placebo- (starch-) treated group. The subjects consumed either HCARE or placebo capsules of 300mg twice daily for 8 weeks. Sexual function was assessed using two psychometric scales, the Female Sexual Function Index (FSFI) Questionnaire and the Female Sexual Distress Scale (FSDS), and by the number of total and successful sexual encounters.
Results: The analysis indicates that treatment with HCARE leads to significantly higher improvement, relative to placebo, in the FSFI Total score (p < 0.001), FSFI domain score for "arousal" (p < 0.001), "lubrication" (p < 0.001), "orgasm" (p = 0.004), and "satisfaction" (p < 0.001), and also FSDS score (p < 0.001) and the number of successful sexual encounters (p < 0.001) at the end of the treatment.
Conclusions: This study demonstrated that oral administration of HCARE may improve sexual function in healthy women. The present study is registered in the Clinical Trial Registry, Government of India, with a number CTRI/2015/07/006045.
Source: Dongre S, Langade D, Bhattacharyya S. “Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study.” Biomed Res Int. (2015);284154.
Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study
Ashwagandha (Withania somnifera) has been described in traditional Indian Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. This pilot study was conducted to evaluate the spermatogenic activity of Ashwagandha root extract in oligospermic patients. Forty-six male patients with oligospermia (sperm count < 20 million/mL semen) were enrolled and randomized either to treatment (n = 21) with a full-spectrum root extract of Ashwagandha (675 mg/d in three doses for 90 days) or to placebo (n = 25) in the same protocol. Semen parameters and serum hormone levels were estimated at the end of 90-day treatment. There was a 167% increase in sperm count (9.59 ± 4.37 × 10(6)/mL to 25.61 ± 8.6 × 10(6)/mL; P < 0.0001), 53% increase in semen volume (1.74 ± 0.58 mL to 2.76 ± 0.60 mL; P < 0.0001), and 57% increase in sperm motility (18.62 ± 6.11% to 29.19 ± 6.31%; P < 0.0001) on day 90 from baseline. The improvement in these parameters was minimal in the placebo-treated group. Furthermore, a significantly greater improvement and regulation were observed in serum hormone levels with the Ashwagandha treatment as compared to the placebo. The present study adds to the evidence on the therapeutic value of Ashwagandha (Withania somnifera), as attributed in Ayurveda for the treatment of oligospermia leading to infertility.
Source: Ambiye VR, Langade D, Dongre S, Aptikar P, Kulkarni M, Dongre A. “Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study.” Evid Based Complement Alternat Med. (2013);2013:571420.
Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial
Background: Withania somnifera (ashwagandha) is a prominent herb in Ayurveda. This study was conducted to examine the possible effects of ashwagandha root extract consumption on muscle mass and strength in healthy young men engaged in resistance training.
Methods: In this 8-week, randomized, prospective, double-blind, placebo-controlled clinical study, 57 young male subjects (18–50 years old) with little experience in resistance training were randomized into treatment (29 subjects) and placebo (28 subjects) groups. Subjects in the treatment group consumed 300 mg of ashwagandha root extract twice daily, while the control group consumed starch placebos. Following baseline measurements, both groups of subjects underwent resistance training for 8 weeks and measurements were repeated at the end of week 8. The primary efficacy measure was muscle strength. The secondary efficacy measures were muscle size, body composition, serum testosterone levels and muscle recovery. Muscle strength was evaluated using the 1-RM load for the bench press and leg extension exercises. Muscle recovery was evaluated by using serum creatine kinase level as a marker of muscle injury from the effects of exercise.
Results: Compared to the placebo subjects, the group treated with ashwagandha had significantly greater increases in muscle strength on the bench-press exercise (Placebo: 26.4 kg, 95 % CI, 19.5, 33.3 vs. Ashwagandha: 46.0 kg, 95 % CI 36.6, 55.5; p = 0.001) and the leg-extension exercise (Placebo: 9.8 kg, 95 % CI, 7.2,12.3 vs. Ashwagandha: 14.5 kg, 95 % CI, 10.8,18.2; p = 0.04), and significantly greater muscle size increase at the arms (Placebo: 5.3 cm2, 95 % CI, 3.3,7.2 vs. Ashwagandha: 8.6 cm2, 95 % CI, 6.9,10.8; p = 0.01) and chest (Placebo: 1.4 cm, 95 % CI, 0.8, 2.0 vs. Ashwagandha: 3.3 cm, 95 % CI, 2.6, 4.1; p < 0.001). Compared to the placebo subjects, the subjects receiving ashwagandha also had significantly greater reduction of exercise-induced muscle damage as indicated by the stabilization of serum creatine kinase (Placebo: 1307.5 U/L, 95 % CI, 1202.8, 1412.1, vs. Ashwagandha: 1462.6 U/L, 95 % CI, 1366.2, 1559.1; p = 0.03), significantly greater increase in testosterone level (Placebo: 18.0 ng/dL, 95 % CI, -15.8, 51.8 vs. Ashwagandha: 96.2 ng/dL, 95 % CI, 54.7, 137.5; p = 0.004), and a significantly greater decrease in body fat percentage (Placebo: 1.5 %, 95 % CI, 0.4 %, 2.6 % vs. Ashwagandha: 3.5 %, 95 % CI, 2.0 %, 4.9 %; p = 0.03).
Conclusion: This study reports that ashwagandha supplementation is associated with significant increases in muscle mass and strength and suggests that ashwagandha supplementation may be useful in conjunction with a resistance training program.
Source: Wankhede, S., Langade, D., Joshi, K., Sinha, S. R., & Bhattacharyya, S. “Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial.” Journal of the International Society of Sports Nutrition (2015), 12, 43.
Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root
Hypoglycemic, diuretic and hypocholesterolemic effects of roots of W. somnifera (ashvagandha) were assessed on human subjects. Six mild NIDDM subjects and six mild hypercholesterolemic subjects were treated with the powder of roots of W. somnifera for 30 days. Suitable parameters were studied in the blood and urine samples of the subjects along with dietary pattern before and at the end of treatment period. Decrease in blood glucose was comparable to that of an oral hypoglycemic drug. Significant increase in urine sodium, urine volume, significant decrease in serum cholesterol, triglycerides, LDL (low density lipoproteins) and VLDL (very low density lipoproteins) cholesterol were observed indicating that root of W. somnifera is a potential source of hypoglycemic, diuretic and hypocholesterolemic agents. Clinical observations revealed no adverse effects.
Source: Andallu B, Radhika B. “Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root.” Indian J Exp Biol. (2000) ;38(6):607-9.
Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in hypercholesteremic rats
Hypocholesteremic and antioxidant effects of Withania somnifera (WS) Dunal (Solanaceae) were investigated in hypercholesteremic male albino rats. When the root powder of WS was added to the diet at 0.75 and 1.5 gm/rat/day, hypercholesteremic animals registered significant decreases in total lipids (-40.54%; -50.69%), cholesterol (-41.58%; -53.01%) and triglycerides (-31.25%; - 44.85%) in plasma. On the other hand, significant increases in plasma HDL-cholesterol levels (+15.10%; +17.71%), HMG-CoA reductase activity (+19.51%; +26.02%) and bile acid content (+24.64%; +30.52%) of liver were noted in these animals. A similar trend was also noted in bile acid (+22.43%;+28.52%), cholesterol (+14.21%; +17.68%) and neutral sterol (+12.40%; +18.85%) excretion in the hypercholesteremic animals with WS administration. Further, a significant decrease in lipid-peroxidation (-35.29%; -36.52%) occurred in WS administered hypercholesteremic animals when compared to their normal counterparts. However, it appeared that WS root powder is also effective in normal subjects for decreasing lipid profiles.
Source: Visavadiya NP, Narasimhacharya AV. “Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in hypercholesteremic rats.” Phytomedicine. (2007);14(2-3):136-42.
Withania somnifera Root Extract Enhances Telomerase Activity in the Human HeLa Cell Line
Aging is a decelerating unidirectional process of life. Shortening of telomeric DNA, the (TTAGGG)n hexanucleotide repeats, which form the caps at the chromosome ends, is implicated to determine the aging process, and more importantly the healthy lifespan itself. Telomerase, a ribonucleoprotein having reverse transcriptase activity, arrests telomere loss through addition of the TTAGGG repeats de novo, to the ends of the chromosome. The telomere/telomerase maintenance is an inevitable necessity to delay aging and for a healthy lifespan. Here, we report the potential of full-spectrum, high concentration Ashwagandha (Withania somnifera), an Ayurvedic medicinal herb, root extract to increase telomerase activity. HeLa cells, when treated with various concentrations of Ashwagandha root extract, showed an increase in telomerase activity measured with the established Telomerase Rapid Amplification Protocol (TRAP) assay. Ashwagandha root extract increased telomerase activity with highest enhancement of ~45% at 10 - 50 μg concentration. Thus, Ashwagandha root extract has the anti-aging inducing potential.
Source: Raguraman, V. and Subramaniam, J. “Withania somnifera Root Extract Enhances Telomerase Activity in the Human HeLa Cell Line.” Advances in Bioscience and Biotechnology (2016), 7, 199-204.
A randomized, double blind placebo controlled study of efficacy and tolerability of Withaina somnifera extracts in knee joint pain
Background: Root extracts of Withania somnifera (Ashwagandha) are known to possess analgesic, anti-inflammatory and chondroprotective effects. An aqueous extract of roots plus leaves of this plant has shown to yield higher percentages of withanolide glycosides and, accordingly, may possess better analgesic, anti-inflammatory and chondroprotective effects than root alone extracts.
Objectives: To evaluate efficacy and tolerability of a standardized aqueous extract of roots plus leaves of W. somnifera in patients with knee joint pain and discomfort.
Material and methods
Sixty patients with knee joint pain and discomfort were randomized in a double-blind manner to W. somnifera 250 mg, W. somnifera 125 mg and placebo, all given twice daily. Assessment was done by Modified WOMAC, Knee Swelling Index (KSI), Visual Analogue Scale (VAS) at baseline and at the end of 4, 8, 12 weeks. Tolerability was assessed by incidence of adverse effects in treatment groups. Student's ‘t’ test and ANOVA were used to compare mean change from baseline within and between the study groups. A p < 0.05 was considered significant.
Results: At the end of 12 weeks, compared to baseline and placebo, significant reductions were observed in mean mWOMAC and KSI in W. somnifera 250 mg (p < 0.001), W. somnifera 125 mg (p < 0.05) groups. VAS scores for pain, stiffness and disability were significantly reduced in W. somnifera 250 mg (p < 0.001), W. somnifera 125 mg (p < 0.01) groups. W. somnifera 250 mg group showed earliest efficacy (at 4 weeks). All treatments were well tolerated.
Conclusions: Both the doses of an aqueous extract of W. somnifera produced significant reduction in outcome variables, with the 250 mg group showing significantly better response. In addition, the therapeutic response appears to be dose-dependent and free of any significant GI disturbances.
Source: Ramakanth, G. S., Uday Kumar, C., Kishan, P. V., & Usharani, P. “A randomized, double blind placebo controlled study of efficacy and tolerability of Withaina somnifera extracts in knee joint pain.” Journal of Ayurveda and integrative medicine (2016), 7(3), 151–157.
- Wan, C.P. et al. 2013. Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity. Acta Pharmacol Sin. 34(4):522–30.
- Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial Choudhary, D., Bhattacharyya, S., & Joshi, K. (2017). Journal of evidence-based complementary & alternative medicine, 22(1), 96-106.
- Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study Dongre, S., Langade, D., & Bhattacharyya, S. (2015). BioMed research international, 2015.
- Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study Ambiye, V. R., Langade, D., Dongre, S., Aptikar, P., Kulkarni, M., & Dongre, A. (2013). Evidence-Based Complementary and Alternative Medicine, 2013.
- Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial Wankhede, S., Langade, D., Joshi, K., Sinha, S. R., & Bhattacharyya, S. (2015). Journal of the International Society of Sports Nutrition, 12(1), 43.