Niacin-bound chromium enhances myocardial protection from ischemia-reperfusion injury

A novel niacin-bound, chromium-based energy formula (EF; InterHealth Nutraceuticals, Benicia, CA) has been developed in conjunction with D-ribose, caffeine, ashwagandha extract (containing 5% withanolides), and selected amino acids. We have assessed the efficacy of oral administration of EF (40 mg x kg body wt(-1) x day(-1)) in male and female rats over a period of 90 consecutive days on the cardiovascular and pathophysiological functions in an isolated rat heart model. After 30, 60, and 90 days of treatment with EF, the hearts of male and female rats were subjected to 30 min of global ischemia followed by 2 h of reperfusion and were measured for myocardial ATP, creatine phosphate (CP), phosphorylated AMP kinase (p-AMPK), and heat shock proteins. Myocardial ATP and CP levels were increased in both male and female rats after EF treatment compared with the controls. Western blot analyses were performed to quantify the expression of stress-related proteins such as heat shock proteins (HSP-70, -32, and -25) and are found to be increased in both male and female rats after EF treatment. The p-AMPK level, which is a sensor for the energy state in various cell types, was also found to be increased after treatment with EF in both male and female rats. Aortic flow, maximum first derivative of developed pressure, left ventricular developed pressure, and infarct size were observed after ischemia-reperfusion and found to be significantly improved in EF-treated rats compared with control animals. Thus EF demonstrated long-term safety as well as exhibiting significant cardioprotective ability during ischemia and reperfusion injury by increased energy production, improved cardiac function, and reduced infarct size.     

Long-term safety evaluation of a novel oxygen-coordinated niacin-bound chromium (III) complex

Chromium (III) is an essential micronutrient required for normal protein, fat and carbohydrate metabolism, as well as helps insulin metabolize fat, turn protein into muscle and convert sugar into energy. A broad spectrum of research investigations including in vitro, in vivo and clinical studies demonstrated the beneficial effects of novel oxygen- coordinated niacin-bound chromium (III) complex (NBC) in promoting glucose-insulin sensitivity, lipid profile, cardioprotective ability and lean body mass. This study examined the long-term safety of NBC by orally administering either 0 or 25 ppm or the human equivalency dose of 1000 microg elemental chromium (III) as NBC per day for 52 consecutive weeks to male and female Sprague-Dawley rats. Animals of each group and each gender were sacrificed on 26, 39, or 52 weeks of treatment. Body weight, physical and ocular health, feed and water intake, selected organ weights as such and as a percentage of liver and brain weight, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluations were conducted. At 26, 39, or 52 weeks of treatment, body weight gain was significantly reduced by 7.7%, 8.1% and 14.9% in male rats, and 5.5%, 11.4% and 9.6% in female rats, respectively, in the NBC treatment groups. No significant changes were observed in hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluation between control and NBC groups at these time points. These findings, thus far, are in agreement with the subchronic studies in terms of the safety of NBC.     

Enhancement of antitumor effect of paclitaxel in combination with immunomodulatory Withania somnifera on benzo(a)pyrene induced experimental lung cancer

The current experimental work deals with the immunomodulatory studies on the extract of Withania somnifera (L.) Dunal root powder against benzo(a)pyrene induced lung cancer in male Swiss albino mice. In our previous study, we reported the antioxidant and anticarcinogenic effect of W. somnifera (L.) Dunal along with paclitaxel. Immune dysfunction has been found to be associated with cancer and chemotherapy. Benzo(a)pyrene induced cancer animals were treated with 400mg/kg bodyweight of W. somnifera (L.) Dunal extract for 30 days significantly alters the levels of immunocompetent cells, immune complexes and immunoglobulins. Based on the data, the carcinogen as well as the paclitaxel affects the immune system, the toxic side effects on the immune system is more reversible and more controllable by W. somnifera (L.) Dunal. These results concluded the immunomodulatory activity of W. somnifera (L.) Dunal extract, which is a known immunomodulator in indigenous medicine.     

Protective effect of Withania somnifera (Solanaceae) on collagen glycation and cross-linking

Modification of collagen such as non-enzymatic glycation and cross-linking plays an important role in diabetic complications and age-related diseases. We evaluate the effect of Withania somnifera on glucose-mediated collagen glycation and cross-linking in vitro. Extent of glycation, viscosity, collagen-linked fluorescence and pepsin solubility were assessed in different experimental procedures to investigate the effect of W. somnifera. Tail tendons obtained from rats (Rattus norvegicus) weighing 250-275 g were incubated with 50 mM glucose and 100 mg of metformin or Withania root powder or ethanolic extract of Withania under physiological conditions of temperature and pH for 30 days. Formation of advanced glycation end products (AGE) was measured by fluorescent method whereas the cross-linking of collagen was assessed by pepsin digestion and viscosity measurements. Tendon collagen incubated with glucose showed an increase in glycation, AGE and cross-linking of collagen. The collagen incubated with W. somnifera and metformin ameliorates these modifications. The ethanolic extract of Withania showed more prominent effect than Withania root powder. The activity of ethanolic extract of Withania is comparable to metformin, a known antiglycating agent. In conclusion, Withania could have therapeutic role in the prevention of glycation induced pathogenesis in diabetes mellitus and aging.     

Seasonal Occurrence of Henosepilachna vigintioctopunctata (F.) (Coleoptera: Coccinellidae) and Its Parasitoid on Ashwagandha in India

The outbreak of Henosepilachna vigintioctopunctata (F.) was noticed on a medicinal plant, Withania somnifera Dunal during 2004-05. The population level of the pest was reached its peak in August. The parasitoid Pediobius foveolatus caused 51.94%±12.20% parasitism. The pest completed its life cycle in 20.15±1.50 days on W. somnifera. The longevity of the male and female adults of the pest was 22.07±3.71 and 31.07±4.38 days, respectively. The gravid females of H. vigintioctopunctata laid an average of 287.64±33.38 eggs during their oviposition period of 10.40±2.80 days.     

Protective effect of Withania somnifera Dunal on the behavioral and biochemical alterations in sleep-disturbed mice (Grid over water suspended method)

Sleep disruption involves extensive changes in physiological function, including EEG, motor, metabolic, autonomic processes physiological homeostasis and psychological balance that are necessary for physical health. Benzodiazepines are the most widely used drugs for the sleep related problems in spite of their limitations and side effects. Objective of the study was to investigate the protective effect of W. somnifera on the behavioral and biochemical alterations in sleep disturbed mice. Pretreatment with W. somnifera root extract (100. 200 mg/kg) and diazepam (0.5 mg/kg) significantly protected reduction in body weight, improved the reduced locomotor activity and anxiety levels in animals. Biochemical studies also revealed that W. somnifera (100 and 200 mg/kg) and diazepam (0.5 mg/kg) pretreatment for five days decreased significantly lipid peroxidation, nitrites levels and improved catalase, and reduced glutathione levels. Co-administration of W. somnifera (100 mg/kg) with diazepam (0.5 mg/kg) improved significantly all the biochemical parameters as compared to their effect per se. Preliminary results suggest that Withania root extract can be used in the management sleep loss and associated oxidative stress.     

Modulation of TCA cycle enzymes and electron transport chain systems in experimental lung cancer

The modulatory effect of Withania somnifera along with paclitaxel on tricarboxylic acid (TCA) cycle key enzymes and electron transport chain complexes were investigated against lung cancer induced by benzo(a)pyrene in Swiss albino mice. Decreased activities of TCA cycle key enzymes such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) in lung cancer bearing animals were observed. Upon W. somnifera along with paclitaxel administration the above biochemical changes were inclined towards normal control animal values. Activities of mitochondrial enzymes and electron transport complexes were analyzed in the experimental groups to determine the efficiency of energy production. This study further confirms the chemotherapeutic effect of W. somnifera along with paclitaxel which is found to be more effective in the treatment of lung cancer. Thus these results are consistent with our hypothesis that the combination chemotherapy of W. somnifera along with paclitaxel as a promising chemotherapeutic agent.     

Suppressive effect of Withania somnifera root powder on experimental gouty arthritis: An in vivo and in vitro study

The effect of Withania somnifera L. Dunal root powder on paw volume and serum lysosomal enzyme activities was investigated in monosodium urate crystal-induced rats. The levels of beta-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal incubated polymorphonuclear leucocytes (PMNL). A significant increase in the level of paw volume and serum lysosomal enzymes was observed in monosodium urate crystal-induced rats. The increased beta-glucuronidase and lactate dehydrogenase level were observed in untreated monosodium urate crystal incubated polymorphonuclear leucocytes. On treatment with the W. somnifera root powder (500/1000 mg/kg body weight), the above changes were reverted back to near normal levels. W. somnifera also showed potent analgesic and antipyretic effect with the absence of gastric damage at different dose levels in experimental rats. For comparison purpose, non-steroidal anti-inflammatory drug (NSAID) indomethacin was used as a standard. These results provide evidence for the suppressive effect of W. somnifera root powder by retarding amplification and propagation of the inflammatory response without causing any gastric damage.     

Curative property of Withania somnifera Dunal root in the context of carbendazim-induced histopathological changes in the liver and kidney of rat.

The liver and kidney of rat underwent severe histopathological lesions when treated with a single bolus dose of carbendazim, a fungicide, particularly affecting the hepatocytes and the renal corpuscles, respectively. The effects appear to be manifestations of the microtubule-disrupting activity of carbendazim. Treatment of carbendazim-treated rats with the powder of tuberous root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure of these organs. The results indicate that Withania somnifera would be an effective curative for carbendazim-induced histopathological changes in the liver and kidney.     

Molecular characterization of India Ginseng Withania somnifera (L) using ISSR markers

Molecular Biology Reports - Ashwagandha (Withania somnifera (L.) Dunal), popularly known as Indian ginseng or winter cherry is a multipurpose plant of immense therapeutic value in the ayurvedic and...     

Compatibility of Inherent Fungal Endophytes of Withania somnifera with Trichoderma viride and its Impact on Plant Growth and Withanolide Content

Journal of Plant Growth Regulation - Withania somnifera (Ashwagandha), also known as Indian ginseng, is an important ancient medicinal plant, used in the Indian traditional systems of medicine. In...     

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.     

Calystegine distribution in some solanaceous species

The distribution of eight calystegines (A(3), A(5), B(1), B(2), B(3), B(4), C(1) and N(1)) and their content was investigated by gas chromatography coupled to mass spectrometry (GC-MS) in Datura metel, Atropa belladonna, Hyoscyamus albus, Mandragora autumnalis, Solanum sodomaeum, Withania somnifera, Withania frutescens and Brunfelsia nitida. The most frequently encountered calystegines were A(3), B(1), B(2) and B(3), while distribution of N(1) and C(1) was more limited. In all the investigated samples, calystegines A(5) and B(4) were never detected. This report focuses for the first time on calystegines in Withania and Brunfelsia genera and in Mandragora autumnalis and Solanum sodomaeum species.     

Long-term metabolic effects of different doses of niacin-bound chromium on Sprague-Dawley rats

We simultaneously assessed benefits and risks of niacin-bound chromium (NBC) intake at varying doses over a prolonged period of time (>1.2 years) in male and female Sprague-Dawley (SD) rats. We performed the study in two phases. First, we followed 60 male and 60 female SD rats, each gender divided into six groups. Through day 150 (phase 1A), all SD rats received a high sucrose diet (30% w/w) with or without different concentrations of NBC. The male/female groups were: 1] control without NBC n = 10, 2] low NBC (2.8 ppm, n = 10), 3] medium NBC (8.7 ppm, n = 20), 4] high NBC (28.0 ppm, n = 20). Based on dosing, we refer to the three treatment groups as 1X, 3X, and 10X. During days 151–312 (phase 1B), NBC was removed from diets of one half of the 3X and 10X groups. These are referred to as 3X satellite and 10X satellite. In phase 2 (days 313–460), males from groups 1X, 3X, 10X, 3X satellite, and 10X satellite received the same 3X dose of NBC (8.7 ppm). The last two groups also ingested different doses of a formulation of natural products in addition to NBC. We examined blood pressure, the renin–angiotensin system (RAS), nitric oxide (NO), and insulin systems and inflammatory parameters. Results in male and female SD rats were comparable. NBC lowered systolic blood pressure (SBP) in a dose-dependent fashion; however, after 200 days, the SBP of the low dose group (1X) began to rise and returned to baseline control. After raising the dose of NBC to 3X, the SBP in the 1X group decreased significantly once more. When half the test rats (3X and 10X) were deprived of NBC, SBP rose gradually to control levels after 2 to 3 months. However, the SBP decreased significantly once more when each satellite group returned to the 3X dose. Special testing suggests that NBC at adequate dosing increases insulin sensitivity, lowers HbA1C, decreases activity of the RAS, at least in part, through ACE inhibition, enhances NO activity, and is without signs of toxicity. The addition of a formula composed of antioxidants and immune modulators to the chromium regimen caused even faster and more profound changes in SBP than with NBC alone. We conclude that NBC at adequate dosing is effective in male and female SD rats on certain metabolic parameters over a prolonged period, effects that disappear over months after NBC is removed. When dosing is returned, the effectiveness of NBC returns. Low doses of NBC may lose their effect over time. No signs of toxicity were observed.     

Neuroprotective Effects of Withania somnifera on 4-Hydroxynonenal Induced Cell Death in Human Neuroblastoma SH-SY5Y Cells Through ROS Inhibition and Apoptotic Mitochondrial Pathway

Neurochemical Research - The antioxidant, anti-inflammatory, and anticancer activities of Withania somnifera (WS) are known for a long time. This study was aimed to examine whether WS also...     

Purification and characterization of a glycoprotein inhibitor of toxic phospholipase from Withania somnifera

A phospholipase inhibitor (WSG) has been purified from Withania somnifera using gel-filtration and ion-exchange chromatographies. The WSG is an acidic glycoprotein. Its molecular mass as determined by SDS-PAGE was 27kDa. It neutralized the enzyme activity and pharmacological properties such as cytotoxicity, edema, and myotoxicity of a multi-toxic Indian cobra venom phospholipase (NNXIa-PLA) but failed to neutralize the neurotoxicity. The glycan part of the molecule does not appear to be involved in any of the pharmacological properties studied. The results suggest that the neutralization of the pharmacological effects of the toxic phospholipase is brought about by inhibition of the enzyme activity by formation of a complex between the WSG and the toxic phospholipase. We report the purification and characterization of a glycoprotein phospholipase A inhibitor from Withania somnifera, medicinal plant.     

Impacts of fish oil on the gut microbiota of rats with alcoholic liver damage

The purpose of this study was to clarify the effects of fish oil on the gut microbiota of rats with alcoholic liver damage. Thirty-six male Wistar rats (8 weeks old) were divided into six groups: C (control), CF25 (control diet with 25% fish oil substitution), CF57 (control diet with 57% fish oil substitution), E (ethanol-containing diet), EF25 (ethanol-containing diet with 25% fish oil substitution), and EF57 (ethanol-containing diet with 57% fish oil substitution) groups. All groups were pair-fed an isoenergetic diet based on the E group. Rats were sacrificed after 8 weeks. Rats in the E group showed significant hepatic injuries including high plasma aspartate transaminase and alanine transaminase activities, hepatic cytokine levels, plasma endotoxin level, and protein expression of the toll-like receptor-4 signaling pathway; moreover, lipid accumulation and inflammation based on histological examinations were also observed. In contrast, these phenomena was ameliorated in rats of the EF25 and EF57 groups. Although the intestinal structure did not change among the groups, alterations in the gut microbiotic composition were observed due to chronic ethanol intake and fish oil replacement such as the Firmicutes-to-Bacteroidetes ratio, Chao-1 index, ACE index, a principal component analysis and linear discriminant analysis of effect size. In terms of the gut-liver axis, this study confirmed that fish oil replacement exerted ameliorative effects on ethanol-induced liver injuries in rats by acting through alterations in the microbiotic composition.     

Notes on Withania (Solanaceae) in Somalia

The identity of Withania reichenbachii is established, the name is neotypified, and the species is described and illustrated. The new combination W. grisea (Hepper & Boulos) Thulin is made. The typification of W. somnifera is discussed, and it is concluded that the present typification can stand. A key to and a synopsis of the four species of Withania now recognised in Somalia are given.     

In vitro withanolide production by Withania somnifera L. cultures

In vitro multiple shoots, root, callus and cell suspension cultures of Withania somnifera exhibited the potentiality to produce pharmacologically active withanolides. Multiple shoots cultures exhibited an increase in withanolide A accumulation compared to shoots of the mother plant. In vitro generated root cultures as well as callus and suspension cultures also produced withanolides albeit at lower levels.