Withania somnifera improves bone calcification in calcium-deficient ovariectomized rats

Osteoporosis, characterized by reduction in bone density, is a significant source of mortality among the elderly, particularly in oestrogen-deficient women. We studied the effect of Withania somnifera (WS) root extract (ethanolic), which contains oestrogen-like withanolides for anti-osteoporotic activity. Female Sprague-Dawley rats were either sham operated (n = 12) or ovariectomized (n = 12) and treated with WS/vehicle (65 mg kg(-1)), orally for 16 weeks (n = 12). All rats were allowed free access to a calcium-deficient diet (0.04% Ca) and distilled water. At termination, urinary excretion of calcium (Ca) and phosphorus (P) and serum levels of Ca, P and alkaline phosphatase (ALP) were measured. Femur and tibia bones were processed for histological (histology), morphological (scanning electron microscopy, SEM), biomechanical strength (impact test) and mineral composition (ash) analysis. Ovariectomized (OVX) rats showed a significant increase in serum ALP levels and urinary Ca and P excretion. Histological findings revealed narrowed, and disappearance of, trabeculae with widened medullary spaces in the OVX group. Ash analysis showed a reduction in ash weight, percent ash, ash Ca, ash P and ash magnesium levels in the OVX group. Further, SEM examination revealed metaphyseal bone loss in femurs and impact test showed a reduction in biomechanical strength of tibias in OVX rats. WS treatment markedly prevented the above changes in OVX rats and thus may be a potential agent in the treatment of osteoporosis.     

Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats

6-Hydroxydopamine (6-OHDA) is one of the most widely used rat models for Parkinson's disease. There is ample evidence in the literature that 6-OHDA elicits its toxic manifestations through oxidant stress. In the present study, we evaluated the anti-parkinsonian effects of Withania somnifera extract, which has been reported to have potent anti-oxidant, anti-peroxidative and free radical quenching properties in various diseased conditions. Rats were pretreated with 100, 200 and 300 mg/kg b.w. of the W. somnifera extract orally for 3 weeks. On day 21, 2 microL of 6-OHDA (10 microg in 0.1% in ascorbic acid-saline) was infused into the right striatum while sham operated group received 2 microL of the vehicle. Three weeks after 6-OHDA injections, rats were tested for neurobehavioral activity and were killed 5 weeks after lesioning for the estimation of lipidperoxidation, reduced glutathione content, activities of glutathione-S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase, catecholamine content, dopaminergic D2 receptor binding and tyrosine hydroxylase expression. W. somnifera extract was found to reverse all the parameters significantly in a dose-dependent manner. Thus, the study demonstrates that the extract of W. somnifera may be helpful in protecting the neuronal injury in Parkinson's disease.     

Treatment of non-insulin-dependent diabetes mellitus

Diabetes mellitus has been declared to be at an epidemic level by the World Health Organization. The syndrome is characterised as either Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. Impaired glucose tolerance for extended periods of time results in serious complications such as kidney damage and impaired blood circulation and is the main cause for blindness and amputations in patients with diabetes. A combination of life-style change, dietary change and oral medications can treat Type II diabetes mellitus effectively and prevent long-term complications. Combination therapy appears to be the most effective approach in controlling blood glucose levels. This review updates the progress made in medicinal chemistry towards promising biological targets, with the development of a new generation of small molecules having improved efficacy and safety profiles.     

Treatment of non-insulin-dependent diabetes mellitus

Diabetes mellitus has been declared to be at an epidemic level by the World Health Organization. The syndrome is characterised as either Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus. Impaired glucose tolerance for extended periods of time results in serious complications such as kidney damage and impaired blood circulation and is the main cause for blindness and amputations in patients with diabetes. A combination of life-style change, dietary change and oral medications can treat Type II diabetes mellitus effectively and prevent long-term complications. Combination therapy appears to be the most effective approach in controlling blood glucose levels. This review updates the progress made in medicinal chemistry towards promising biological targets, with the development of a new generation of small molecules having improved efficacy and safety profiles.     

Evaluation of anti-inflammatory effect of Withania somnifera root on collagen-induced arthritis in rats

Context: Withania somnifera (Linn.) Dunal (Solanaceae) has long been used as an herb in Ayurvedic and indigenous medicine and has received intense attention in recent years for its chemopreventive properties.

Objective: The present study focuses on the effect of W. somnifera root powder on the behavioral and radiological changes in collagen-induced arthritic rats.

Materials and methods: The rats were randomly divided into five groups: normal control, arthritic control, arthritic rats treated with W. somnifera root powder (at dose levels 600 and 800?mg?kg^?1) and arthritic rats treated with methotrexate (at dose level 0.3?mg?kg^?1). The treatment with W. somnifera (daily) and methotrexate (weekly) was initiated from the 20th day post collagen immunization and continued up until the 45th day. Arthritis was assessed macroscopically by measuring paw thickness, ankle size and body weight. Arthritic pain was assessed by toe-spread and total print length of the affected paw. Functional recovery due to the oral treatment of W. somnifera and methotrexate was assessed by sciatic functional index and rota rod activity.

Results: Administration of W. somnifera root powder (600?mg?kg^?1) to the arthritic rats significantly decreased the severity of arthritis by effectively suppressing the symptoms of arthritis and improving the functional recovery of motor activity and radiological score.

Discussion and conclusion: W. somnifera root has a protective effect against collagen-induced arthritis (CIA) in rats. The results suggest that W. somnifera root powder acts as an anti-inflammatory and antioxidant agent in decreasing the arthritic effects in collagen-induced arthritic rats.     

Prenatal developmental toxicity evaluation of Withania somnifera root extract in Wistar rats

Context: Withania somnifera (L) Dunal (Solanaceae) is an important traditional herbal medicine used for thousands of years and is considered as the Indian ginseng. Reports on the effect of Withania somnifera root (WSR) extract on the developing foetus of pregnant rats including mortality, structural abnormalities, changes in growth and effects on dams are not available. Objective: The present study was performed to evaluate the prenatal developmental toxicity potential of WSR extract in rats. Materials and methods: WSR extract was given orally to pregnant rats during the period of major organogenesis and histogenesis (days 5 to 19 of gestation) at the dose levels of 500, 1000 and 2000?mg/kg/day. Clinical observations including mortality, moribundity, behavioural changes, signs of overt toxicity, body weight, gross pathological changes of dams and foetal analyses including external malformations, skeletal and soft tissue malformations were evaluated. Results: No evidence of maternal or foetal toxicity was observed. WSR extract caused no changes (p?Discussion and conclusion: Under the conditions of the study, the no-observed-effect level (NOEL) of WSR extract for maternal and developmental toxicity was concluded to be at least 2000?mg/kg/day.     

前列地尔对非胰岛素依赖型糖尿病病人胰岛素及血小板聚集率的影响

目的：探讨前列地尔对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）病人胰岛素及血小板聚集率的影响。方法：应用前列地尔２００μｇ加入０．９％氯化钠注射液５００ｍＬ中静脉滴注，ｑｄ×１０ｄ，治疗５０例ＮＩＤ ＤＭ病人（男性２３例，女性２７例，年龄５８±ｓ１０ａ）。治疗前后测定空腹胰岛素、餐后２ｈ胰岛素及血小板聚集率。结果：前列地尔刺激胰岛素分泌增加和降低血小板聚集率。治疗后的餐后２ｈ胰岛素显著增加（Ｐ＜０．０１），血小板聚集率显著下降（Ｐ＜０．０１，Ｐ＜０．０５）。结论：前列地尔增加ＮＩＤＤＭ病人的胰岛素分泌，降低血小板聚集率     

NIDDM患者冠心病与胰岛素抵抗之间关系的探讨

探讨ＮＩＤＤＭ病人冠心病与胰岛素抵抗之间的关系。方法；通过比较男性ＮＩＤＤＭ合并ＣＨＤ者与未合并ＣＨＤ者的血糖，血胰岛素水平，胰岛素敏感指数，血脂，细胞内Ｃａ＾２＋和Ｍｇ６２＋浓度，并对上述诸因素与ＣＨＤ的关系进行多因素Ｌｏｇｉｓｔｉｃ逐步回归分析。     

二甲双胍治疗非胰岛素依赖型糖尿病

目的：观察二甲双胍对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）的疗效。方法：２８例ＮＩＤＤＭ病人（男性１７例，女性１１例，年龄５８±ｓ１０ａ），在用足量的磺酰脲类降糖药无效时加用二甲双胍，开始剂量为２５０～５００ｍｇ／ｄ，根据血糖调整剂量，最大剂量为１．５ｇ／ｄ。治疗３ｍｏ。结果：空腹和餐后２ｈ血糖、糖基化血红蛋白和２４ｈ尿糖均明显降低（Ｐ＜０．０１）。空腹血糖和餐后２ｈ血糖控制总有效率为８９％。有腹泻和恶心各３例。结论：二甲双胍治疗ＮＩＤＤＭ病人效果满意。     

Pharmacological Studies on Leaves of Withania somnifera.

Anti-inflammatory activity and protective effect against CCl (4)-induced hepatotoxicity of alcoholic extract of leaves of WITHANIA SOMNIFERA have been assessed. The leaves were found to possess marked effects in subacute inflammation and hepatotoxicity. A comparison of the anti-inflammatory properties revealed the extract at 1 g/kg dose to be as active as 50 mg/kg of phenylbutazone and 10 mg/kg of hydrocortisone. The protective effect of the extract at 1 g/kg dose against CCl (4)-induced hepatotoxicity was comparable to 10 mg/kg of hydrocortisone.     

格列喹酮治疗非胰岛素依赖型糖尿病

非胰岛素依赖型糖尿病有２５例（男性１３例，女性１２例；年龄６１±ｓ１０ａ），用格列喹酮治疗，开始剂量１５－９０ｍｇ／ｄ，根据血糖调整剂量，最大量为２７０ｍｇ／ｄ。治疗３ｍｏ。结果：空腹和餐后２ｈ血糖、糖基化血红蛋白和２４ｈ尿糖均明显降低（Ｐ＜０．０１）。空腹和餐后２ｈ血糖控制总有效率为８０％。２例有轻度恶心。该药为安全有效的降糖药。     

格列齐特治疗非胰岛素依赖性糖尿病的疗效

本文对国产和进口格列齐特各治疗８１和７６例非胰岛素依赖性糖尿病进行为期３－４ｍｏ的疗效对比。结果：２组的空腹和餐后血糖、ＨｂＡ１及血清三酰甘油（甘油三酯）明显降低，但空腹和餐后血清胰岛素和血清胆固醇没有明显变化。国产格列齐特的有效剂量明显低于进口格列齐特（Ｐ＜０．０５）。本文证明两者的疗效没有明显差别。     

Effect of Withania somnifera on Sleep-Wake Cycle in Sleep-Disturbed Rats: Possible GABAergic Mechanism

Sleep deprivation disrupts significantly sleep pattern and cause poor quality of sleep. The aim the present study was to explore role of Withania somniferra root extract in sleep-disturbed rats. Male wistar rats (n=5-6/group) were sleep deprived for 24 h using grid suspended over water method. Withania somniferra extract (100 mg/kg) was administered intraperitoneally (i.p.) 30 min before actual recording (EEG and EMG) recording and electrophysiological recordings are further classified as- sleep latency, slow wave sleep, paradoxical sleep, total sleep, wakefulness. One day (24 h) sleep deprivation delayed latency sleep, reduced duration of slow wave sleep, rapid eye movement sleep, total sleep time and increased total waking as compared to animals placed on saw dust (P<0.05). Pretreatment with Withania somniferra extract (100 mg/kg) and diazepam (0.5 mg/kg) significantly improved electrophysiological parameters, which was further reversed by picrotoxin (2 mg/kg) and potentiated by muscimol (0.05 mg/kg). Flumazenil (2 mg/kg) did not produce any significant effect on the sleep parameters of Withania somnifera root extract. Present study suggests the involvement of GABAergic mechanism in the sleep promoting effect of Withania somniferra in sleep-disturbed state.     

格列齐特治疗非胰岛素依赖型糖尿病

观察６０例Ⅱ型糖尿病病人服用格列齐特的国产与法国产２种制剂的近期疗效。结果：两者对Ⅱ型糖尿病均有明显降血糖作用，不良反应轻微，在其他磺酰脲类药物治疗无效时，格列齐特仍可有明显疗效。无论是２组组间比较还是自身对照比较，两者的降糖作用，有效剂量，维持剂量和疗效反应都十分相近。     

Improvement in insulin sensitivity by losartan in non-insulin-dependent diabetic (NIDDM) rats.

The present investigation was undertaken to study the effects of chronic treatment with losartan (2 mg kg(-1)/ day P.O) in neonatal non-insulin-dependent diabetes mellitus (NIDDM) rats. To induce NIDDM single-dose injection of STZ (70 mg kg(-1); i.p.) was given to 5 day old pups. The animals were weaned at 30 days and after a period of 3 months, they were checked for fasting and fed glucose levels to confirm the status of NIDDM. Losartan (2 mg kg(-1); p.o.) was administered for 6 weeks into the confirmed diabetic rats. A group of control animals were also maintained and this group received saline 5 days after birth. Fasting and fed glucose levels in NIDDM rats were significantly higher than control rats. Treatment with losartan in the NIDDM rats caused a significant decrease in insulin levels and reduction in elevated fasting and fed glucose levels. Results of the oral glucose tolerance test (OGTT) showed a significant increase in AUC(glucose)and AUC(insulin)values in NIDDM control rats. Losartan treatment significantly decreased both AUC(glucose)and AUC(insulin)values. Insulin sensitivity (K(ITT)) index of NIDDM control was significantly low as compared to Wistar control animals followed by significant increase in T(1/2)glucose value. Losartan treatment significantly reversed both K(ITT)and T(1/2)glucose value. Our data indicates that losartan increases insulin sensitivity in NIDDM rats.     

Long-term effects of glipizide on insulin secretion and blood glucose control in patients with non-insulin-dependent diabetes mellitus

Summary Of 23 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose fasting blood glucose had not reached 6.0 mmol·l^–1 after 10 weeks of dietary regulation, 15, who had had a weight reduction of –2.8 kg by dietary control, did achieve a fasting blood glucose 6.0 mmol·l^–1 after addition of 20 mg glipizide daily. They had a sustained (2 years) increase in meal-induced insulin secretion (32% increase in postprandial C-peptide AUC), and a sustained reduction in postprandial hyperglycaemia (34% reduction in AUC). Ten of the patients took a mean daily dose <5mg (4.8 mg) and had a sustained increase in insulin secretion rate (increased C-peptide slope). The 15 patients had no elevation of basal insulin secretion and no impairment of weight reduction. The remaining 8 subjects, who showed little or no weight reduction on dietary control, had little or no reduction in fasting blood glucose despite long-term treatment with 20 mg glipizide daily, a less sustained increase in meal-induced insulin secretion, a smaller reduction of postprandial hyperglycaemia, and an increase in body weight. On diagnosis the 8 subjects did not differ from the other 15 subjects in age, body weight, blood glucose, HbA₁c, C-peptide or insulin, nor in their glucose and insulin responses to a test dose of glipizide; the main reason for the apparent drug failure appeared to be deficient compliance with dietary regulation rather than a primary inability to respond to sulphonylurea treatment. The findings indicate that glipizide is able to promote and maintain increased meal-induced insulin secretion and near-normal fasting and non-fasting blood glucose levels without continuous B cell stimulation. However, these improvements prevail mainly in subjects who persist with hypocaloric dietary regulation.     

Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats

1. Stroke causes brain injury in millions of people worldwide each year. Despite the enormity of the problem, there is currently no approved therapy that can reduce infarct size or neurological disability. One of the approaches that can be used in limiting the neurological damage after stroke is the use of prophylactic treatment in patients with a high-risk of stroke. The present study was undertaken to investigate the effect of the Indian herbal plant Withania somnifera as a prophylactic treatment in the middle cerebral artery (MCA) occlusion model of stroke in rats. 2. Two groups of male Wistar rats were pretreated with a hydroalcoholic extract of W. somnifera (1 g/kg, p.o.) for 15 and 30 days. Thereafter, rats were subjected to focal ischaemia by occlusion of the MCA using an intraluminal thread. After 2 h MCA occlusion, reperfusion was allowed by retracting the thread. Animals were assessed for ischaemic changes using diffusion-weighted imaging 30 min after reperfusion. Twenty-four hours later, rats were subjected to motor performance tests and were subsequently killed for the estimation of the marker of oxidative stress malondialdehyde (MDA). The control group received vehicle and a similar protocol was followed. 3. Significant motor impairment, with elevated levels of MDA, was observed in vehicle-treated MCA-occluded rats. In addition, diffusion-weighted imaging showed increased signal intensity in the right hemisphere compared with the contralateral hemisphere. Treatment with W. somnifera for 15 days did not improve motor performance or decrease the elevated levels of MDA. However, when the pretreatment time of W. somnifera was increased to 30 days, it prevented motor impairment and significantly decreased the raised levels of MDA compared with vehicle-treated rats. In the W. somnifera (30 days)-pretreated group, the percentage hemispheric lesion area in diffusion-weighted imaging was significantly attenuated (17 +/- 2%) compared with the vehicle-treated MCA-occluded group (30 +/- 4%). 4. Because W. somnifera has been documented to have anti-oxidant properties, the protection afforded by W. somnifera could be due to its anti-oxidant effect. The present study provides first evidence of the effectiveness of an Indian herb in focal ischaemia.     

Therapeutic effect of Withania somnifera on pristane-induced model of SLE

Systemic lupus erythematosus commonly known as lupus is an intricate disorder with multiple organ involvement characterized primarily by inflammation caused due to deposition of immune-complexes formed by production of autoantibodies against nuclear, nucleolar as well as cytoplasmic self-antigens. Lack of availability of suitable treatments or treatments that are only symptomatic calls for investigation of possible modalities. Withania somnifera with its immunomodulatory properties is prescribed for arthritis in ayurveda. In the present study, the therapeutic effect of Withania somnifera pure root powder (at 1,000 and 500 mg/kg body weight) on pristane-induced Balb/c model of lupus was investigated to elucidate its remedial outcome on SLE. SLE-like symptoms are produced in the model of lupus: production of autoantibodies, proteinuria, nephritis as well as immune-complex deposition along with various other inflammatory markers such as formation of lipogranuloma, production of pro-inflammatory cytokines including interleukin-6 and tumor necrosis factor-α, nitric oxide and reactive oxygen species. Withania somnifera was found to have potent inhibitory effect on proteinuria, nephritis and other inflammatory markers. Humoral response, however, was found to be impervious. The potent reduction in inflammation in the present model of lupus suggests further investigation of this herb for its possible therapeutic use in SLE.     

Production of withaferin A in shoot cultures of Withania somnifera

Multiple shoot cultures of Withania somnifera were established from single shoot tip explants and their potential for the production of two principle withanolides, withaferin A and withanolide D was investigated. Shoot tips grown on MS medium supplemented with BA (1 mg l(-1)) induced 10.0 +/- 1.15 microshoots per explants and shoot cultures accumulated both withanolides (withaferin A = 0.04%, withanolide D = 0.06%). Supplementation of MSSM (solid) agar medium with 4% sucrose enhanced accumulation of both withaferin A (0.16%) and withanolide D (0.08%). Reduction of the agar concentration to 0.16% increased the number of microshoots induced per explant to 25.5. MSSM liquid medium containing 10% coconut milk favoured a maximum increase in biomass (27 fold); number of microshoots induced (37.6 +/- 1.45) as well as accumulation of withaferin A (0.14%).