Acute and subacute toxicity studies of a poly herbal formulation used for diabetes.

Objectives: PHF-dia (Poly Herbal Formulation Diabetes) is a polyhedral formulation possessing antihyperglycemic and antihyperlipdimic effects. This study aims to assess acute and sub-acute toxicity of PHF-dia in rats. Methods: This is an experimental study conducted in two different phases. Acute toxicity was conducted for 14 days and sub-acute toxicity was conducted for 28 days. Both studies were conducted in animal house of Jinnah University for Women, Karachi, Pakistan. Acute toxicity was evaluated in vivo with single time oral administration of 400 mg/kg and 2000 mg/kg doses for two weeks. Sub-acute toxicity was investigated with the application of repeated doses of 150 mg/kg/day, 250 mg/kg/day and 500 mg/kg/day for 28 days. Results: Acute toxicity study results showed no toxic symptoms, behavioral changes or death in rats up to 2000 mg/kg. Therefore, LD50 of oral toxic dose must be more than 2000 mg/ml. Similarly, sub-acute toxicity studies confirmed the safety of PHF-dia and showed no clinical symptoms nor biochemical or histological variation in rats treated with 150 mg/kg, 250 mg/kg and 500 mg/kg compared to the control group (p <0.05). Conclusion: This indicates safe nature of PHF-dia for the further clinical trials. However, mechanism of action of PHF-dia is not fully understood.

Development of herbal formulation of medicinal plants and determination of its antihyperuricemic potential in vitro and in vivo rat's model.

Hyperuricemia is a common metabolic disorder and several herbal formulations are being used for its treatment. The study aimed to develop herbal formulation (Urinil B) and find its hypouricemic effects in vitro and in vivo. Urinil B was prepared by taking Trachyspermum ammi, Piper nigrum and Berberis vulgaris equally. In vitro Dissolution test and xanthine oxidase inhibition assay was performed for checking capsule absorbance and IC50 calculation respectively. For in vivo experimentation, the study comprised of 14 groups of rats (n=6). Results showed that significant xanthine oxidase inhibition was shown by herbal formulation with IC50 of 586±1.5µg/mL. Oral administration of Urinil B 250, 500 and 1000 mg/kg decreased serum and liver uric acid levels of hyperuricemic rats in dose and time dependent manner. 3 day and seven day administration of Urinil B reduced serum and liver uric acid level more significantly as compared to one day administration. However, allopurinol normalized serum and liver uric acid levels in all study groups. The present study indicated marked hypouricemic effects of Urinil B in hyperuricemia induced by potassium oxonate in rats. However, due to caveat of small sample size in this study, clear conclusion regarding hypouricemic potential of Urinil B can't be made.

Nardostachys chinensis Batalin: A review of traditional uses, phytochemistry, and pharmacology.

Nardostachys chinensis Batalin (Valerianaceae) has been widely used in different traditional systems of medicine, including Islamic, Ayurvedic, Chinese, and Korean folk medicine. It has been used in traditional medicine as a tranquilizer, hepatotonic, cardiotonic, diuretic, and analgesic. Preliminary in vitro and in vivo studies have provided valuable scientific evidence for its traditional uses. This review aims to summarize reported traditional uses, phytochemistry, and pharmacological potential of N. chinensis while identifying potential areas of further research of plant. The review comprises literature pertaining to the pharmacological potential and phytochemistry of N. chinensis using worldwide accepted scientific databases via electronic search (Elsevier, Google Scholar, Pub Med, Scopus, Springer, Wiley online library). Moreover, data from ethno botanical text books available in library and electronic search were also included. The Plant List and Kew Herbarium Catalogue databases were used to authenticate the scientific name. Different pharmacological experiments in many in vitro and in vivo models have proved the potential of N. chinensis, namely, anti-inflammatory, anticonvulsant, antibacterial, antihypertensive, antifungal, neuroprotective, cardioprotective, aldose reductase inhibition, and antioxidant activities. The plant contains sesquiterpenenes of various varieties including aristolane, guaiane, and nardosinane types. Moreover, it also contains coumarins, phenols, lignans, neolignans, and glycosides. Reported activities suggested that there may be pharmacological potential for developing N. chinensis as a drug for infections, hypertension, cardiac diseases, Alzheimer's disease, insomnia, epilepsy, cancer, gastric, and liver diseases. More toxicological studies should be performed that will aid the progress to clinical trial studies of N. chinensis.

Anti-Hyperuricemic and Uricosuric Potential of Berberis vulgaris in Oxonate-Induced Hyperuricemic Rats.

Hyperuricemia is a metabolic disorder with characteristic elevated serum uric acid. Recently, several plant-based medicines are being used for the treatment of hyperuricemia. The study aimed to find the hypouricemic potential of Berberis vulgaris in in-vitro and in-vivo study models. In i n-vitro studies, xanthine oxidase inhibition assay was performed to evaluate IC50 value and capsule absorbance of the drug, respectively. For in-vivo experiment, the study comprised 15 groups of rats. In-vitro results revealed that significant xanthine oxidase inhibition was shown by Berberis vulgaris with an IC50 value of 272.73±.3 µg/mL. Similarly, oral administration of Berberis vulgaris with dosages of 250 and 500 mg/kg decreased serum and liver uric acid levels significantly in a dose- and time-dependent manner in oxonate-induced hyperuricemic rats. Furthermore, 3-day and 7-day administration of Berberis vulgaris showed more potential compared to 1-day administrations. The present study indicated marked hypouricemic effects of Berberis vulgaris in rats. Due to caveat of the small sample size, a firm assumption of the hypouricemic effect of Berberis vulgaris cannot be made. However, extensive study is needed to find out the exact molecular mechanism involved and to translate its effects into clinical trials for the further validation of the results.

In vitro and in vivo anti-diabetic activity of Citrullus colocynthis pulpy flesh with seeds hydro-ethanolic extract.

Background Diabetes is the one of the leading cause of morbidity and mortality. Traditionally phytotherapy is widely being used for diabetes treatment and highly valued. Citrus colocynthis has known anti-diabetic potential. However, anti-diabetic potential of hydro-ethanolic extract of C. colocynthis pulpy flesh with seeds is not reported yet. Methods The extract of C. colocynthis pulpy flesh with seeds was done by maceration method using 70% ethanol. To evaluate anti-diabetic and antioxidant potential of the seeded fruit in vitro, α-glucosidase and DPPH inhibition assays was done, respectively. In vivo study used streptozotocin (STZ) induced diabetes model of rats. Rats were randomized in five groups i. e. normal control, negative control, standard control, C. colocynthis 150 and 300 mg/kg. STZ was administered to all groups except normal control. After wards, plant extract and glibenclamide is continued for 14 days. Blood samples were collected from rat tail vein daily and from Cardiac puncture at the end of study. The blood glucose levels were monitored daily by using one-touch blood glucose monitoring system. The blood glucose level was monitored on 0, 1st, 5th, 8th, 11th, and 14th day of induction. Results Hydro-ethanolic extract of C. colocynthis pulpy flesh with seeds was able to decolorize DPPH and therefore possess antioxidant potential, continuous administration for 14 days showed a marked decrease in serum glucose levels (p 0.01) it is found to be somewhat less effective as glibenclamide (standard control) (p 0.001). A time-dependent decrease in blood glucose levels was observed (351.3 ± 4 to 258 m/kg). Conclusion Hydro-ethanolic extract of C. colocynthis pulpy flesh with seeds lowered the serum triglyceride and cholesterol levels in diabetic rats significantly as compared to negative control. The hypoglycemic effect of hydro-ethanolic extract of C. colocynthis pulpy flesh with seeds is may be due to α-glucosidase inhibition potential.

Effects of dietary supplementations and herbs on migraine - a systematic review.

Background Migraine is a disabling disease and conventional treatment has many side effects. Dietary supplements and various herbs have reported valuable effects on migraine. Aim The present study systematically review the effects of these dietary supplements and herbs on migraine. Methods The literature search was done on electronic databases PubMed, Google Scholar and Science direct (2005-2015). The quality of articles was assessed through a criteria list of methodological quality assessment of randomized controlled trials (RCTs). The papers got C50 points considered to be of good quality methodology. The maximum score was 100. Results Fourteen RCTs on migraine were included in this review. The range of quality score varied from 37 to 65 points. Conclusion Various RCTs suggested that dietary and vitamin supplementation and different herbs might be effective in treatment of migraine. Evaluated RCTs have various methodological shortcomings. So, a firm conclusion can't be made for the efficacy of dietary supplementation and herbs in the treatment of migraine.

Pharmacophores Modeling in Terms of Prediction of Theoretical Physicochemical Properties and Verification by EXPERIMENTAL correlations of Carbacylamidophosphates (CAPh) and Sulfanylamidophosphates (SAPh) Tested as New Carbonic Anhydrase Inhibitors.

BACKGROUND: The function of Carbonic anhydrase is to facilitate the physiological process i.e. interconversion of CO2 to HCO3 - by hydration. Carbonic anhydrase enzyme plays a vital role in different physiological processes to regulate pH as well as regulate the inner environment of CO2 and secretion of electrolytes. METHODS: Six representatives of amidophosphate derivatives (L1-L6) were synthesized and evaluated for their biological activities against carbonic anhydrase enzyme. RESULTS: Out of six derivatives, L1 (IC50 = 12.5 ± 1.35 µM), and L2 (IC50 = 3.12 ± 0.45 µM) showed potent activity against BCA-II. While (L3, L4 and L5) showed weak inhibitory activity with IC50 values of 24.5 ± 2.25, 55.5± 1.60, and 75.5 ± 1.25 µM, respectively and were found to be weak inhibitors of carbonic anhydrase as compared to acetazolamide (IC50 =0.12± 0.03µM), used as standard inhibitor. A computational Petra/Osiris/Molinspiration/DFT (POM/DFT) based model has been expanded for the determination of physicochemical parameters governing the bioactivity amidophosphate derivatives (L1-L6) containing (O1 --- O2) pharmacophore site. The six compounds (L1-L6) analyzed here were previously experimentally and now virtually screened for their anti-carbonic anhydrase activity. CONCLUSION: The highest anti-carbonic anhydrase activity was obtained for compound L2, which exhibited excellent bioactivity (% of inhibition = 95%), comparable to acetazolamide (% of inhibition = 89%). The compound L3 represents increased activity as compared to its analogues (L4-L6). The increase of bioactivity from L3 to L4-L6 could be attributed to the presence of a minimum of steric effect of substituents of P=O moiety which plays a decisive template part in the organization of anti-carbonic anhydrase (O1---O2) phramacophore site. Moreover, it is inexpensive, has little side effects and possible inclusions in selective anti-carbonic anhydrase agents design.

In vivo evaluation of antipyretic effects of some homeopathic ultra-high dilutions on Baker's yeast-induced fever on Similia principle.

BACKGROUND: Homeopathy is a controversial alternative system of medicine. The action of homeopathic medicines is considered slow and it is assumed that homeopathic medicines are ineffective in acute conditions such as fever. OBJECTIVE: In the present study, effects of 3 homeopathic medicines on baker's yeast induced fever were investigated. MATERIALS AND METHODS: 42 local strain rabbits were equally divided into 7 groups. Normal saline was orally administered to group 1 (normal control) rabbits without fever induction. Group 2 underwent baker's yeast-induced fever (negative control). Groups 3, 4, 5, 6 and 7 underwent baker's yeast-induced fever and were thereafter treated orally with paracetamol, Nux vomica 200C and 1M, Calcarea phos 200C and Belladonna 200C respectively. Rectal temperature was checked hourly. The abdominal writhing and frequency of loose stools were also monitored. ANOVA was applied for checking statistical significance. p ≤ 0.05 was considered significant. RESULTS: The rectal temperature increased significantly (p < 0.05) in the negative control group when compared to the normal control. Abdominal writhing and loose stools monitoring showed increased writhing and loose stools frequency of group 2, 3, 6 and 7 rabbits. However, treatment of paracetamol significantly reduced rectal temperature. Group 4 & 5 showed significant reduction of rectal temperature together with abatement of abdominal writhing and loose stools. CONCLUSION: N. vomica ultra-high dilutions have normalized rectal temperature and prevented the abdominal writhing and loose stools in baker's yeast-induced fever model of rabbits. It could be due to antidotal activity of N. vomica ultra-high dilutions. Therefore, N. vomica ultra-high dilutions can be useful antipyretic agents and can treat conditions associated with gastrointestinal symptoms. However, fixed conclusion can't be asserted due to caveat of small sample size.

Evaluation of antipyretic activity of Belladonna and Pyrogenium ultrahigh dilutions in induced fever model.

Background Belladonna and Pyrogenium are commonly used to treat fever in homeopathy. But in vivo antipyretic activity of these medicines is not reported yet. The study was conducted to evaluate the effectiveness of ultrahigh dilutions of Belladonna (Bell) and Pyrogenium (Pyro) in fever model of rabbits induced by Baker's yeast. Methods Healthy, local strain rabbits (♂ and ♀) were divided into seven groups (n=42): Normal control, negative control, standard control, pyro 1000c, pyro 200c, Bell 1000c and Bell 200c. Fever was induced by intra peritoneal injection of 135 mg/kg Baker's yeast suspension. Rectal temperature was measured hourly. All the medicines were administered once a day. The results were expressed as mean ± SEM. ANOVA and least significant difference post hoc test were applied for checking the level of significance, p-value of ≤0.05 was considered significant statistically. Results Pyro in both potencies significantly reduced fever in rabbits compared to negative control group, while both potencies of Bell were ineffective. Paracetamol and Pyro 1000c reduced by 1.2 °C (39.7 ± 0.1 to 38.5 ± 0.1), while Pyro 200c reduced by 1 °C temperature (39.7 ± 0.5 to 38.7 ± 0.2). Conclusions Pyro possesses marked antipyretic activity in rabbit's Baker's yeast fever model. It would embolden its clinical use in fever with more guarantee of its efficacy. However, caveat of small sample size necessitates replication of experiment in large sample size.

Phytochemistry and pharmacological potential of Cassia absus - a review.

OBJECTIVES: Cassia absus is a plant of the family fabaceae with Ayurvedic ethnomedical records. It is used in traditional medicine for the treatment of bronchitis, asthma, cough, conjunctivitis, leucoderma, renal and hepatic diseases, constipation, tumors, venereal ulcer, headache, hemorrhoids and wound healing. Preliminary in vitro and in vivo studies have provided valuable scientific evidence for its use. This review aims to summarize reported pharmacognosy, traditional uses, phytochemistry and pharmacological potential of C. absus while identifying potential areas of further research of plant. KEY FINDINGS: The review comprises literature pertaining to the evidence base therapeutic potential, pharmacognosy and phytochemistry of C. absus spanning from 1935 to 2016 using published articles in peer-reviewed journals, ethno botanical text books, and worldwide accepted scientific databases via electronic search (Elsevier, Google Scholar, PubMed, Scopus, Springer, Web of Science, Wiley online library). Kew Botanical Garden databases and the Plant List were used to authenticate the scientific names. Different pharmacological experiments in many in-vitro and in-vivo models have proved the potential of C. absus with antihypertensive, antifertility, antifungal, anti-inflammatory, anti-hyperglycemic, anti-glycation, antibacterial activity, α- amylase inhibitory activity, antioxidant and reducing activitity etc. chaksine, iso-chaksine, saturated and unsaturated fatty acids, chrysophanol, aloe-emodin and a wide range of chemical compounds have also been reported. Toxicity studies reveal the nontoxic nature of C. absus at a dose of 2000 mg/kg, however, plant possess reproductive toxicity and can be used as birth control or abortifacient. SUMMARY: Reported activities suggest that there is sufficient pharmacological potential for developing C. absus as a drug for hypertension, infections, diabetes and its complications. However, heterogeneity in study protocol and conflicting results mask the ability to replicate these studies. So, future studies should be replicated in line with best practices. More toxicological studies would aid the progress to clinical trial studies. Various ethno medical uses of C. absus have not been evaluated yet.

Pharmacological and nutritive potential of Euphorbia granulata.

Background Euphorbia granulata is herb of family Euphorbiaceae having several traditional uses. The aim of the study is to summarize reported nutritional and medicinal value along with ethnomedical records. Methods The papers on nutritional and medicinal value of E. granulata are collected from electronic search engines (Google Scholar, PubMed). Synonyms are confirmed from "The plant List." Results Pharmacological studies suggest that the extracts of E. granulata possess antioxidant, antibacterial, antifungal, diuretic, antiulcerative colitis and spasmolytic properties. Moreover, it is rich with nutritive components such as carbohydrates, lipid contents (saturated and unsaturated fatty acids), minerals and protein (amino acids). Toxicological data of E. granulata showed that it may be poisonous and toxic at higher doses. Conclusion Research studies suggest that E. granulata has sufficient pharmacological potential against several diseases including infections, gastric ulcers, anuria, oliguria and spasmodic disorders; however, more research is required to confirm its pharmacological potential. Moreover, dose fixation studies should be carried out to avoid its toxicity.

Preliminary phytochemical analysis and in vivo evaluation of antipyretic effects of hydro-methanolic extract of Cleome scaposa leaves.

Cleome scaposa has been associated with the prevention of many diseases as fever, abdominal complaints and cancer. But its antipyretic effect is not reported so far. The aim of this study was to assess the efficacy of C. scaposa in reducing temperature in Baker's yeast-induced fever model of rabbits. Rabbits were randomized into 4 groups (n = 24). Fever was induced in by Saccharomyces cerevisae (3 mL/kg of 10% suspension subcutaneous) in all study groups. Afterward, group 1, 2, 3 and 4 were orally administered with paracetamol 150 mg/kg b. wt., distilled water, C. scaposa 250 and 500 mg/kg b. wt. respectively. 500 mg/kg dosage was selected after dose fixation study. The standard control was paracetamol. Rectal temperature was recorded with the help of a digital thermometer. ANOVA followed by post hoc test was applied for statistical analysis of results. Results of the study indicate that C. scaposa possesses antipyretic activity comparable to that of standard drug paracetamol as it exhibited comparable antipyretic potential against baker's yeast-induced fever in rabbits. This study confirms the traditional use of C. scaposa in fever. So, it can be an alternative therapeutic choice in fever. However, specific constituents responsible for its antipyretic activity should be evaluated.

Effects of homoeopathic ultrahigh dilutions of Aconitum napellus on Baker's yeast-induced fever in rabbits.

OBJECTIVE: To evaluate the effects of homoeopathic ultrahigh dilutions of Aconitum napellus in Baker's yeast-induced fever in rabbits. METHODS: Rabbits were divided into 4 groups and each group contained 6 rabbits. Baker's yeast suspension (20%) was injected subcutaneously. After fever induction, paracetamol and homoeopathic ultrahigh dilutions (A. napellus 200c and 1 000c) were given orally. Rectal temperature was measured with digital thermometer hourly. RESULTS: Fever was induced in all the rabbits after 4 hours of Baker's yeast administration. A. napellus 200c and 1000c significantly reduced the temperature (P < 0.05). In positive control, temperature decrease was more significant (P < 0.001). CONCLUSION: The above findings indicate the effectiveness of ultrahigh dilutions of A. napellus in Baker's yeast-induced fever in rabbits. However, the effects were slower and less significant than standard medicine. Moreover, future research is required to know their mechanism of reducing temperature.

Evaluación del potencial antioxidante de algunas tinturas madre homeopáticas / Evaluation of the antioxidant potential of some homeopathic mother tinctures

Objetivos: en sistemas homeopáticos de medicina, las tinturas madre se prescriben para varias enfermedades y especialmente para condiciones sépticas y la cura de muchos padecimientos. Este estudio se llevó a cabo para evaluar el potencial antioxidante y antibacterial de las diez tinturas madre homeopáticas que se utilizan con mayor frecuencia. Materiales y métodos: diez tinturas madre fueron preparadas y puestas a prueba contra cinco bacterias de importancia clínica patogénica en los humanos (Sal­ monella typhi [ST], Escherichia coli [EC], Bacillus subtilis [BS], Straphylococus aureus [SA], y Pseudomonas aeruiginosa [PA]) mediante el método de microdilución con ciprofloxacina como control positivo. La actividad antioxidante se estimó con un ensayo de inhibición 2,2-difenil-1-picrilhidrazilo (DPPH). El ácido ascórbico se tomó como estándar positivo en actividad antioxidante. Resultados: todas las tinturas madre mostraron cierto nivel de actividad antibacterial. Chinchona officinalis tuvo la actividad máxima (inhibición del 89%) contra Salmonella typhi que las demás tinturas madre en el estudio. Pulsatilla nigricans mostró la inhibición más alta de DPPH (85%) entre las demás tinturas madre de origen vegetal. Conclusión: este estudio revela que las tinturas madre ya mencionadas tienen potencial antibacteriano y antioxidante contra el microorganismo particular y 2,2-difenil-1-picrilidracil (DPPH), respectivamente. (AU)