Mohd Mujeeb

A review on therapeutic potential of Nigella sativa: A miracle herb

Nigella sativa (N. sativa) (Family Ranunculaceae) is a widely used medicinal plant throughout the world. It is very popular in various traditional systems of medicine like Unani and Tibb, Ayurveda and Siddha. Seeds and oil have a long history of folklore usage in various systems of medicines and food. The seeds of N. sativa have been widely used in the treatment of different diseases and ailments. In Islamic literature, it is considered as one of the greatest forms of healing medicine. It has been recommended for using on regular basis in Tibb-e-Nabwi (Prophetic Medicine). It has been widely used as antihypertensive, liver tonics, diuretics, digestive, anti-diarrheal, appetite stimulant, analgesics, anti-bacterial and in skin disorders. Extensive studies on N. sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilator, hepato-protective, renal protective, gastro-protective, antioxidant properties, etc. Due to its miraculous power of healing, N. sativa has got the place among the top ranked evidence based herbal medicines. This is also revealed that most of the therapeutic properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil. The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics, chemical composition and pharmacological activities of the seeds of this plant.

A pharmacological appraisal of medicinal plants with antidiabetic potential

Diabetes mellitus is a complicated metabolic disorder that has gravely troubled the human health and quality of life. Conventional agents are being used to control diabetes along with lifestyle management. However, they are not entirely effective and no one has ever been reported to have fully recovered from diabetes. Numerous medicinal plants have been used for the management of diabetes mellitus in various traditional systems of medicine worldwide as they are a great source of biological constituents and many of them are known to be effective against diabetes. Medicinal plants with antihyperglycemic activities are being more desired, owing to lesser side-effects and low cost. This review focuses on the various plants that have been reported to be effective in diabetes. A record of various medicinal plants with their established antidiabetic and other health benefits has been reported. These include Allium sativa, Eugenia jambolana, Panax ginseng, Gymnema sylvestre, Momrodica charantia, Ocimum sanctum, Phyllanthus amarus, Pterocarpus marsupium, Trigonella foenum graecum and Tinospora cordifolia. All of them have shown a certain degree of antidiabetic activity by different mechanisms of action.

Protective effects of Pycnogenol® on hyperglycemia-induced oxidative damage in the liver of type 2 diabetic rats

Abnormal regulation of glucose and impaired carbohydrate utilization that result from a defective or deficient insulin are the key pathogenic events in type 2 diabetes mellitus (T2DM). Experimental and clinical studies have shown the antidiabetic effects of Pycnogenol (PYC). However, the protective effects of PYC on the liver, a major metabolic organ which primarily involves in glucose metabolism and maintains the normal blood glucose level in T2DM model have not been studied. The present study evaluated the beneficial effect of PYC, French maritime pine bark extract, on hyperglycemia and oxidative damage in normal and diabetic rats. Diabetes was induced by feeding rats with a high-fat diet (HFD; 40%) for 2 weeks followed by an intraperitoneal (IP) injection of streptozotocin (STZ; 40 mg/kg; body weight). An IP dose of 10mg/kg PYC was given continually for 4 weeks after diabetes induction. At the end of the 4-week period, blood was drawn and the rats were then sacrificed, and their livers dissected for biochemical and histopathological assays. In the HFD/STZ group, levels of glycosylated hemoglobin (HbA1c), significantly increased, while hepatic glycogen level decreased. PYC supplementation significantly reversed these parameters. Moreover, supplementation with PYC significantly ameliorated thiobarbituric reactive substances, malonaldehyde, protein carbonyl, glutathione and antioxidant enzymes [glutathione-S-transferase, catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase] in the liver of HFD/STZ rats. These results were supported with histopathological examinations. Although detailed studies are required for the evaluation of the exact protective mechanism of PYC against diabetic complications, these preliminary experimental findings demonstrate that PYC exhibits antidiabetic effects in a rat model of type 2 DM by potentiating the antioxidant defense system. These finding supports the efficacy of PYC for diabetes management.

Enhanced transdermal delivery of an anti-hypertensive agent via nanoethosomes: Statistical optimization, characterization and pharmacokinetic assessment

The aim of the current investigation is to develop and statistically optimize nanoethosomes for transdermal valsartan delivery. Box-Behnken experimental design was applied for optimization of nanoethosomes. The Independent variables were phospholipids 90G (X(1)), ethanol (X(2)), valsartan (X(3)) and sonication time (X(4)) while entrapment efficiency (Y(1)), vesicle size (Y(2)) and flux (Y(3)) were the dependent variables. The optimized formulation obtained was then tested in rats for an in vivo pharmacokinetic study. Results indicate that the nanoethosomes of valsartan provides better flux, reasonable entrapment efficiency, more effectiveness for transdermal delivery as compared to rigid liposomes. Optimized nanoethosomal formulation with mean particle size is 103 ± 5.0 nm showed 89.34 ± 2.54% entrapment efficiency and achieved mean transdermal flux 801.36 ± 21.45 μg/cm(2)/h. Nanoethosomes proved significantly superior in terms of, amount of drug permeated in the skin, with an enhancement ratio of 43.38 ± 1.37 when compared to rigid liposomes. Confocal laser scanning microscopy revealed an enhanced permeation of Rhodamine-Red loaded nanoethosomes to the deeper layers of the skin as compared to conventional liposomes. In vivo pharmacokinetic study of nanoethosomal transdermal therapeutic system showed a significant increase in bioavailability (3.03 times) compared with oral suspension of valsartan. Our results suggest that nanoethosomes are an efficient carrier for transdermal delivery of valsartan.

Role of novel terpenes in transcutaneous permeation of valsartan: effectiveness and mechanism of action

Context: The greatest obstacle for transdermal delivery is the barrier property of the stratum corneum. Many approaches have been employed to breach the skin barrier; the most widely used one is that of chemical penetration enhancers. Of the penetration enhancers, terpenes are arguably the most highly advanced and proven category. Objective: The aim of this investigation was to study effectiveness and mechanism of seven novel terpenes, namely iso-eucalyptol, β-citronellene, valencene, rose oxide, safranal, lavandulol acetate, and prenol, as potential penetration enhancers for improved skin permeation of valsartan through rat skin and human cadaver skin (HCS) with reference to established terpene eucalyptol. Methods: Skin permeation studies were carried out using Automated Transdermal Diffusion Cell Sampling System (SFDC 6, LOGAN Instruments Corp., NJ) on rat skin and HCS. The mechanism of skin permeation enhancement of valsartan by terpenes treatment was evaluated by Fourier transform infrared spectroscopy (FT-IR) analysis, differential scanning calorimetry (DSC) thermogram, and histopathological examination. Results and discussion: Among all study enhancers, iso-eucalyptol produced the maximum enhancement via rat skin [enhancement ratio (ER) = 7.4] and HCS (ER = 3.60) over control. FT-IR spectra and DSC thermogram of skin treated with aforesaid terpenes indicated that permeation occurred due to the disruption of lipid bilayers. No apparent skin irritation (erythema, edema) was observed on treatment with terpenes except β-citronellene, safranal, lavandulol acetate, and prenol, which caused mild irritation. Conclusion: It is concluded that the iso-eucalyptol can be successfully used as safe and potential penetration enhancer for enhancement of skin permeation of lipophilic drug such as valsartan.

Interactions between novel terpenes and main components of rat and human skin: mechanistic view for transdermal delivery of propranolol hydrochloride.

The purpose of this study was to investigate the effectiveness and mechanism(s) of percutaneous absorption of propranolol hydrochloride (PHCL) across rat and human cadaver skin using seven novel terpenes with reference to marker terpene 1,8-cineole. In-vitro skin permeation studies were carried out via rat and human skin models. The mechanism of skin permeation of PHCL by terpenes was evaluated by FTIR, DSC, activation energy measurement and histopathological examination. Amongst the new terpenes, 1,4-cineole was found to be most effective enhancer for diffusion of PHCL through rat skin (ER=3.07) and human cadaver skin (ER=2.42) as compared to control. FTIR spectra and DSC thermogram of skin treated with aforesaid terpenes indicated that permeation occurred due to the disruption of lipid bilayers. No apparent skin irritation (erythema, edema) was observed on treatment of skin with terpenes, the irritation was higher with the β-citronellene and rose oxide. It was concluded that 1,4-cineole can be successfully used as potential permeation enhancer for PHCL. It enhanced the absorption of hydrophilic drug by extraction and disruption of lipid bilayers and keratin denaturation of stratum corneum.

Ellagic acid, an NF-κB inhibitor, ameliorates renal function in experimental diabetic nephropathy.

Diabetic nephropathy (DN) is a serious complication confronted by diabetic patients. Available data indicate that the development of DN is linked to inflammation. In this context, nuclear factor-kappa B (NF-κB) has received much attention. Ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione), found abundantly in plant extracts and fruits, possesses numerous medicinal properties. We investigated the nephroprotective effects of oral treatment of ellagic acid in high fat diet/low dose streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rats. Ellagic acid treatment for 16weeks post induction of diabetes significantly attenuated renal dysfunction and oxidative stress. Ellagic acid significantly inhibited the renal NF-кB activation. Moreover, ellagic acid significantly lowered renal pathology and suppressed transforming growth factor-beta (TGF-β) and fibronectin expressions in renal tissues. Ellagic acid also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α). In cultured rat NRK 52E proximal tubular epithelial cells, ellagic acid treatment inhibited high glucose-induced activation of NF-κB and pro-inflammatory cytokine synthesis. These results suggest that ellagic acid exhibited renal protective effect in diabetic rats partly through antihyperglycemia which was accompanied by attenuation of inflammatory processes via inhibition of NF-κB pathway.

Sedative, antiepileptic and antipsychotic effects of Viscum album L. (Loranthaceae) in mice and rats

ETHNOPHARMACOLOGICAL RELEVANCE Viscum album L. is claimed in traditional medical practice, to be useful in the treatment of epilepsy and insomnia in Himachal Pradesh, India. MATERIALS AND METHODS The effect of Viscum album L. on epilepsy, psychosis and sedative activity was evaluated in mice and rats using standard procedure. RESULTS The aqueous leaf extract of Viscum album L. prolonged the pentobarbital induced sleeping time and reduced the locomotor activity in actophotometer. This suggests that reduced locomotor activity facilitate GABAergic transmission. In addition the extract reduced MES, INH and PTZ-induced convulsions which suggest that there may be possibility of blocking Na(+) channels, opening of Cl(-) channels or enhancing the GABAergic system. The extract decreased the apomorphine-induced stereotyped behavior and potentiates the HAL-induced cataleptic score which suggests the extract possess antidopaminergic activity. CONCLUSION The results obtained in present study suggested that title plant exhibited sedative, antiepileptic and antipsychotic activity in mice and rats.

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-кB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway.

Enhanced glycemic control, pancreas protective, antioxidant and hepatoprotective effects by umbelliferon-α-D-glucopyranosyl-(2I → 1II)-α-D-glucopyranoside in streptozotocin induced diabetic rats

ObjectiveThe objective of the present study was to evaluate the effect of umbelliferon-α-D-glucopyranosyl-(2I → 1II)-α-D-glucopyranoside (UFD) from Aegle marmelos Corr. on serum glucose, lipid profile and free radical scavenging activity in normal and STZ (streptozotocin) induced diabetic rats.Materials and methodsDiabetes was induced by single interperitoneal injecting of streptozotocin (60 mg/kg, i.p.) in the rats. All the rats were divided into following groups; I - nondiabeteic, II - nondiabetic + UFD (40 mg/kg, p.o.), III - diabetic control, IV - UFD (10 mg/kg, p.o.), V - UFD (20 mg/kg, p.o.), VI - UFD (40 mg/kg) and VII - glibenclamide (10 mg/kg, p.o.). Serum glucose level and body weight were determined periodically. Biochemical parameter, antioxidant enzyme and histopathology study were performed on the day 28. Oral glucose tolerance test study was performed to identify the glucose utilization capacity.ResultsAll the doses of UFD and glibenclamide decrease the level of serum glucose, glycated hemoglobin, glucose-6-phosphatase, fructose-1-6-biphosphate and increased the level of plasma insulin, hexokinase. The UFD doses also showed effects on antioxidant enzymes viz. superoxide dismutase, catalase and glutathione peroxidase which were significantly increased and the level of malonaldehyde was markedly decreased. Histologically study, focal necrosis, deposition of fats, increased the size of the intercalated disc were observed in the diabetic rat liver, kidney, heart and pancreas but was less obvious in treated groups. The mechanism of action of the UFD emerges to be due to increase the activity of antioxidant enzyme and secretion of pancreatic insulin.ConclusionReduction in the FBG (fasting blood glucose), glycated hemoglobin, glucose-6-phosphatase, fructose-1-6-biphosphate, superoxide dismutase, catalase, glutathione peroxides, cholesterol, triglyceride, LDL, VLDL levels and improvement in the level of the plasma insulin, hexokinase, HDL was observed by the UFD treated rats. The result indicates that UFD has anti-diabetic activity along with anti hyperlipidemic and antioxidant efficacy and provides a scientific rationale to be used as an Anti-diabetic agent.