Ethnomedicinal importance of Patuletin in Medicine: Pharmacological Activities and Analytical Aspects.

BACKGROUND: Plant-derived bioactive molecules have been a major source of therapeutics for human and veterinarian purposes. Different traditional medicine system across the globe had relied on natural resources to meet their demand of healthcare. Still in modern world pharmaceutical industries look for phytochemicals to develop new drugs. The current review explores patuletin, a flavonoid for its diverse reported pharmacological activities along with its analytical techniques. METHODS: Scientific data published on patuletin was collected from Scopus, Science Direct, Pubmed, Google, and Google Scholar. The collected data were analyzed and arranged as per specific pharmacological activities performed using in-vitro or in-vivo methods. Analytical methods of patuletin have been presented next to pharmacological activities, Results: Available scientific literature indicates patuletin has anti-inflammatory, cytotoxic, genotoxic, hepatoprotective, antiproliferative, antiplatelet, antinociceptive, and antioxidant activity. In addition to these activities, its biological potential on breast cancer, rheumatoid arthritis, aldose reductase, and different types of microorganisms has been also presented in this work. Analytical data on patuletin signified the importance of patuletin for the standardization of herbal products and derived medicine. CONCLUSION: It may be concluded that patuletin with its diverse biological activities and readily available analytical methods, holds the potential to be translated into a new drug entity.

Nephroprotective effect of Apium graveolens L. against Cisplatin-induced nephrotoxicity.

BACKGROUND: Cisplatin is extensively used in treating cancers, and its primary side-effect is nephrotoxicity. It accumulates in proximal convoluted tubules where it promotes cellular damage by oxidative stress, apoptosis, and inflammation, etc. In Unani medicine, Tukhm-e-Karafs(Apium graveolens L.) (TK) is mentioned in the literature to manage various kidney ailments due to its diuretic and deobstruent activities. OBJECTIVE: To investigate the nephroprotective effects of powder of TK in Cisplatin-induced nephrotoxicity in an animal model and to validate the Unani claim of its nephroprotective action. MATERIAL AND METHODS: In curative protocol, cisplatin (5 mg/kg body weight i.p) was administered on day one and powder of TK (500 and 1000 mg/kg p.o.) from the sixth day onwards for ten days. TK (500 and 1000 mg/kg p.o.) was given for ten days and Cisplatin (5 mg/kg body weight i.p) on day 11 in the protective model. At the end of the study, all the animals were sacrificed, and renal biochemical parameters were determined. KIM-1 level was also investigated in the kidney homogenate in conjunction with histopathological inspection of kidney tissues. RESULTS: Significant increase in serum creatinine and BUN, presence of mononuclear cell infiltration, tubular dilation and vacuolation in renal histopathology, and increased KIM-1 level confirmed the nephrotoxicity due to Cisplatin. TK's administration protects the kidney as suggested by the changes in biochemical renal function, decreased level of KIM-1, and improvement in histopathological changes. CONCLUSION: The result advocated that TK prevented renal injury and maintained normal renal function in both models. It may be due to improved clearance of Cisplatin from kidney tubules and reduction in reactive oxygen species (ROS) produced by the inflammatory response.

Obesity Potentiates the Risk of Drug-Induced Long QT Syndrome - Preliminary Evidence from WNIN/Ob Spontaneously Obese Rat.

Drug-induced long QT syndrome (DI-LQTS) is fatal and known to have a higher incidence in women rather than in men. Multiple risk factors potentiate the incidence of DI-LQTS, but the actual contribution of obesity remains largely unexplored. Correspondingly, the present study is aimed to evaluate the susceptibility of DI-LQTS in WNIN/Ob rat in comparison with its lean counterpart using 3-lead electrocardiography. Four- and eight-month-old female WNIN/Ob and their lean controls were used for the experimentation. Non-invasive blood pressure measurement and total body electric conductivity (TOBEC) analysis were carried out. After the baseline evaluations, animals were anesthetized with Ketamine (50 mg/kg). Haloperidol (12.5 mg/kg single dose) was administered intraperitoneally and ECG was taken at 0, 10, 20, 30, 60 min, and 24 h time points. Myocardial lystes were used to assess the BNP, protein carbonylation, and hydroxyproline content. Adiposity, as assessed by TOBEC, is higher in obese rats with elevated mean arterial blood pressure. Baseline-corrected QT interval (QTc) is significantly higher in the obese rat with a wider QRS complex. The incidence of PVC and VT are more intense in the obese rat. Haloperidol-induced QT prolongation in obese rats was rapidly induced than in lean, which was observed to remain till 24 h in obese groups while normalized in lean controls. Higher levels of BNP, protein carbonylation, hydroxyproline content, and relative heart weights indicated the presence of cardiac hypertrophy. The study provides preliminary evidence that obesity can be a potential risk factor for DI-LQTS with faster onset and longer subsistence.

A traditional poly-herbal formulation improves cognitive function in C57BL/6 mice / Una formulación tradicional de poli-hierbas mejora la función cognitiva en ratones C57BL / 6

INTRODUCTION: Khamira Gawzaban Ambari Jadwar Ood Saleeb Wala (KGAJOS) is a polyherbal compound Unani Pharmacopoeial formulation described in traditional Unani texts as Muqawwi-e-Aza-e-Raeesa (tonic for brain, heart, liver and stomach). KGAJOS is reported to possess anxiolytic and antidepressant activity in mice. Though it is used clinically for various neurological conditions, preclinical efficacy of this formulation in learning and memory enhancement / improvement is not established. METHOD: KGAJOS was evaluated for cognitive function improvement activity using Morris water maze test in C57BL/6 mice. Piracetam was used as positive control for comparison. Anymaze video tracking software was used for tracking the path of mice in pool as per standard protocol. RESULTS: During probe trial in Morris water maze test, a significant increase in time spent in platform quadrant was observed at 1000 and 1500 mg/kg bw of KGAJOS (p < 0.01 and 0.001, respectively) as well as in piracetam group (p < 0.01) compared to vehicle control. Latency to reach the platform quadrant (escape latency) was significantly reduced (p < 0.001) in piracetam and KGAJOS group at 1000 and 1500 mg/kg bw compared to vehicle control. No change in time spent in platform quadrant and escape latency was observed at 500 mg/kg bw of KGAJOS. CONCLUSIONS: Morris water maze experiment conducted in mice revealed improved learning and memory function of KGAJOS at the dose levels of 1000 and 1500 mg/kg bw whereas 500 mg/kg bw was not found to be effective. Observed efficacy of KGAJOS confirmed the traditional claims and usage of this formulation in conditions associated with cognition and memory

INTRODUCCIÓN: Khamira Gawzaban Ambari Jadwar Ood Saleeb Wala (KGAJOS) es una formulación de Unani compuesto de poliherbal descrito como tónico para el cerebro, corazón, hígado y estómago. Este estudio se realizó para evaluar la eficacia preclínica de KGAJOS en el aprendizaje y la memoria. MÉTODO: Se evaluó la actividad de mejora de la función cognitiva de KGAJOS utilizando la prueba de laberinto de agua de Morris en ratones C57BL / 6. Se utilizó piracetam como control positivo. Se utilizó el software de seguimiento de video Anymaze para rastrear la ruta. RESULTADOS: Durante la prueba de la sonda, se observó un aumento significativo en el tiempo empleado en el cuadrante de la plataforma a 1000 y 1500 mg / kg de peso corporal de KGAJOS (p < 0,01 y 0,001, respectivamente) y en el grupo de piracetam (p < 0,01) en comparación con el control. La latencia para alcanzar el cuadrante de la plataforma (latencia de escape) se redujo significativamente (p < 0,001) en el grupo de piracetam y KGAJOS a 1000 y 1500 mg / kg de peso corporal en comparación con el control. CONCLUSIONES: El experimento del laberinto de agua de Morris reveló una mejora en la función de aprendizaje y memoria con 1000 y 1500 mg / kg de peso corporal de KGAJOS, mientras que 500 mg / kg de peso corporal no fue efectivo. La eficacia observada de KGAJOS confirmó las afirmaciones tradicionales y el uso de esta formulación en condiciones asociadas con la cognición y la memoria

Oxidative stress in Vitiligo patients and administration of Munzij and Mushil therapy, a poly herbal Unani formulation - hospital-based study.

Background Vitiligo, a skin disorder is viewed as a multifactorial process with major role of reactive oxygen species in concert to destroy or incapacitate melanocytes. In Unani system of medicine the treatment of Bars (Vitiligo) starts with removal of harmful materials from the body with Munzij and Mushil (MM), a poly herbal Unani formulation. Methods Herein, oxidative stress related parameters as MDA, SOD, GPx and CAT have been estimated in the 21 clinically diagnosed Vitiligo in-patients and subsequently these parameters were evaluated during and after administration of MM therapy and compared with 21 healthy subjects. Results There was significant difference in the parameters viz., SOD (p<0.001) and CAT (p<0.005) activity at the baseline with no statistical significant difference in MDA and GPx activity among Vitiligo subjects and controls. After MM therapy there was no statistical significant difference among the values of these parameters in Vitiligo subjects. Conclusions The results suggest that there is imbalance in the oxidant-antioxidant status of Vitiligo subjects and the MM therapy is not found to significantly change the levels of oxidative stress related parameters.

Cabazitaxel and silibinin co-encapsulated cationic liposomes for CD44 targeted delivery: A new insight into nanomedicine based combinational chemotherapy for prostate cancer.

Cancer stem cells (CSCs) are the promising targets for cancer chemotherapy that cannot be eliminated by conventional chemotherapy. In this study cationic liposomes of cabazitaxel (CBX) and silibinin (SIL) were prepared with an aim to kill cancer cells and CSCs for prostate cancer. CBX act as cancer cell inhibitor and SIL as CSC inhibitor. Hyaluronic acid (HA), an endogenous anionic polysaccharide was coated on cationic liposomes for targeting CD44 receptors over expressed on CSCs. Liposomes were prepared by ethanol injection method with particle size below 100 nm and entrapment efficiency of more than 90% at 10% w/w drug loading. Liposomes were characterized by dynamic light scattering, transmission electron microscopy, 1H nuclear magnetic resonance and scanning electron microscopy-energy dispersive x-ray spectroscopy. Liposomes were evaluated for their anticancer action in androgen independent human prostate cancer cell lines (PC-3 and DU-145). HA coated liposomes showed potential cytotoxicity over other groups with low IC50, significantly inhibited cell migration and induced apoptosis. Synergistic cytotoxic effect was also observed with HA coated liposomes that resulted in colony formation inhibition and G2/M phase arrest. Proficient cytotoxicity against CD44+ cells (14.87 ± 0.41% in PC-3 and 33.95 ± 0.68% in DU-145 cells) indicated the efficiency of HA coated liposomes towards CSC targeting. Hence, the outcome of this combinational therapy with CD44 targeting indicates the suitability of HA coated CBX and SIL co-loaded liposomes as a potential approach for eradicating prostate cancer and herein might provide a insight for future studies.

Compensation to clinical trial participants in India: A gap analysis.

The recent amendments notified by the Government of India, for conducting clinical trial, is greatly appreciable as promoting safety and well-being of human subjects. These rules clearly state that medical management of injuries in clinical trials is mandatory, and clinical trial-related injury or death needs to be compensated over and above the medical management. These rules need to be reconsidered for simplification and better understanding of issues regarding compensation. There is a need of clarity at some points which should be discussed with all stakeholders for better understanding of current regulations. In our view, attention must also be given to academic investigators, during discussion to promote availability of cost-effective treatment in India.

Comparative toxicity study on classical and modified version of Jawarish Jalinoos (a traditional Unani formulation) in rats.

BACKGROUND: Jawarish Jalinoos (JJ) is a classical semisolid traditional Unani formulation clinically used for the treatment of weakness of vital organs, liver, and stomach. Although JJ has been widely used clinically for several decades, no scientific report is available for its safety. METHODS: JJ and its sugar-free tablet version (SFJJ; formulated to target diabetic population) were assessed for safety in rats. Ninety-day repeated dose oral toxicity study was performed as per the Organisation for Economic Co-operation and Development Guideline 408. JJ was orally administered at the dose of 2000 mg/kg bw/d, whereas SFJJ was orally administered at the doses of 506 mg/kg body weight (bw)/d, 1012 mg/kg bw/d, and 2024 mg/kg bw/d for 90 days. The animals were periodically observed for clinical signs of toxicity, mortality, morbidity, body weight changes, and feed consumption. At the end of the study, hematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight, and histological examination were performed. RESULTS: Treatment with SFJJ and JJ showed no significant differences in body weight gain, feed consumption, hematology, clinical biochemistry, and serum electrolytes. No gross pathological findings and differences in relative organ weights were observed between control and drug treated rats. Histological examination revealed no toxicologically significant abnormalities related with SFJJ or JJ treatment. CONCLUSION: The 90-day repeated dose oral toxicity study demonstrates that the no observed adverse effect level of SFJJ and JJ is greater than 2024 mg/kg bw/d and 2000 mg/kg bw/d (p.o.) in rats, respectively. Both formulations were found to be safe up to the tested dose levels and experimental conditions, and therefore safe for clinical use as specified in the literature.

Beneficial effect of Hypericum perforatum on depression and anxiety in a type 2 diabetic rat model.

Recent studies have revealed diverse therapeutically interesting pharmacological properties of a standardized Hypericum perforatum extract (HpE) potentially useful for treatments of patients with metabolic and psychiatric disorders. Consequently, the presented experiments were designed to test usefulness of the extract for the treatment of comorbid conditions of mood disturbances and anxiety in diabetic rats. Type 2 diabetes mellitus was induced in overnight fasted rats by a single i.p. injection of streptozotocin (STZ; 65 mg/kg), 15 min after an i.p. injection of nicotinamide (120 mg/kg). HpE was administered orally (100 and 200 mg/kg b.w..) to diabetic animals for 14 days. Anxiolytic activity was evaluated using open-field exploration test (OFT) and elevated plus maze (EPM) test. Antidepressant activity was assessed using Porsolt's forced swim test (FST). Fasting blood glucose levels in different groups were analyzed on the 14th day. Diabetic rats showed significant increase in anxiety in OFT and EPM compared to non diabetic normal control rats. Diabetic rats treated with HpE have shown significant anxiolytic activity in OFT and EPM test. In FST, immobility period of vehicle treated diabetic rats was significantly increased (p < 0.05) compared to normal control rats. Treatment with HpE significantly decreased (p < 0.001) immobility period compared to vehicle treated diabetic control rats. HpE treatment significantly reduced elevated blood glucose levels in diabetic rats. The presented observations strongly suggest that HpE could be suitable alternative therapeutic option for prevention, as well as treatment, of comorbidities caused by, or associated with, depression, anxiety and diabetes.

Hypolipidemic and Antiobesity-Like Activity of Standardised Extract of Hypericum perforatum L. in Rats.

Hypericum perforatum is known to have diverse medicinal uses for centuries. The antidepressant activity of Hypericum perforatum is widely accepted and proved in both animal and clinical studies. Present study was undertaken to investigate the effect of Hypericum perforatum in a battery of animal models for metabolic disorder. Hypericum is tested for hypolipidemic activity in normal rats, antiobesity activity in high-fat-diet induced obese rats, and fructose-fed rats. Hypericum was orally administered as suspension in 0.3% carboxymethyl cellulose at the doses of 100 and 200 mg/kg body weight for 15 consecutive days. Hypericum significantly lowered total cholesterol and low-density cholesterol in normal rats. Hypericum significantly inhibited weight gain in high-fat-fed rats. In fructose-fed rats, Hypericum normalised the dyslipidemia induced by fructose feeding and improved the insulin sensitivity. Taken together, Hypericum could be the antidepressant therapy of choice for patients suffering from comorbid diabetes and obesity.

Antidiabetic activity of standardized extract of Quassia amara in nicotinamide-streptozotocin-induced diabetic rats.

The aim of the present study was to evaluate the efficacy of a standardized methanol extract of Quassia amara L. (Family: Simaroubaceae) in nicotinamide-streptozotocin-induced diabetic rats. Non insulin dependent diabetes mellitus was induced by streptozotocin in rats pre-treated with nicotinamide. Diabetic rats were treated with oral doses of Quassia amara extract (QaE; 100 and 200 mg/kg) or glibenclamide (10 mg/kg; as standard). QaE and glibenclamide were administered as a suspension in 0.3% carboxy methyl cellulose for 14 days. Control animals received an equal volume of vehicle. Blood samples were collected by retro-orbital puncture on day 14, 1 h after last treatment. Plasma glucose, insulin and lipid parameters (total cholesterol, LDL-C, HDL-C and triglycerides) were measured using commercially available biochemical kits. The oral glucose tolerance test was performed to evaluate the effect of the extract on peripheral glucose utilization in normal rats. Both doses of QaE significantly (p < 0.01) reduced elevated fasting blood glucose levels in diabetic rats. In the oral glucose tolerance test, QaE treatment significantly increased (p < 0.05) the glucose tolerance compared with the vehicle. QaE and glibenclamide, effectively normalized dyslipidemia associated with streptozotocin-induced diabetes. The findings of the present study indicate that Quassia amara extract may be potentially valuable in the treatment of diabetes and associated dyslipidemia.