Immunopathogenesis of urticaria: a clinical perspective on histamine and cytokine involvement.

BACKGROUND: Urticaria is a clinical condition characterized by the appearance of wheals (hives), angioedema, or both. Over the last several decades, a better understanding of the mechanisms at play in the immunopathogenesis of urticaria has underscored the existence of numerous urticaria subtypes. Separating the different kinds of urticaria explicitly helps find the best detection method for the management of this skin disorder. Subtypes of urticaria also include both spontaneous and physical types. The conventional ones include spontaneous urticaria, constituting both acute and chronic urticaria. Therefore, a broad and effective therapy is essential for the diagnosis and treatment of urticaria. METHODS: To understand the immunopathogenesis of urticaria, various databases, including PubMed, Scopus, and Web of Science, were used to retrieve original articles and reviews related to urticaria. While information on several clinical trials were obtained from clinicaltrials.gov database. RESULTS: This article highlights the immunopathogenesis involved in the intricate interaction between cellular infiltration, immune reactions, coagulation cascades, and autoantibodies that underlie urticaria's pathophysiology. CONCLUSION: The recent progress in understanding urticaria can help to understand the intricate characteristics in the immunopathogenesis of urticaria and could play a beneficial role in the management of urticaria.

Development process of a clinical guideline to manage type 2 diabetes in adults by Ayurvedic practitioners.

Background: Type 2 diabetes mellitus (T2DM), a common chronic health condition, has major health and socioeconomic consequences. In the Indian subcontinent, it is a health condition for which individuals commonly consult Ayurvedic (traditional medical system) practitioners and use their medicines. However, to date, a good quality T2DM clinical guideline for Ayurvedic practitioners, grounded on the best available scientific evidence, is not available. Therefore, the study aimed to systematically develop a clinical guideline for Ayurvedic practitioners to manage T2DM in adults. Methods: The development work was guided by the UK's National Institute for Health and Care Excellence (NICE) manual for developing guidelines, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, and the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. First, a comprehensive systematic review was conducted which evaluated Ayurvedic medicines' effectiveness and safety in managing T2DM. In addition, the GRADE approach was used for assessing the certainty of the findings. Next, using the GRADE approach, the Evidence-to-Decision framework was developed, and we focused on glycemic control and adverse events. Subsequently, based on the Evidence-to-Decision framework, a Guideline Development Group of 17 international members made recommendations on Ayurvedic medicines' effectiveness and safety in T2DM. These recommendations formed the basis of the clinical guideline, and additional generic content and recommendations were adapted from the T2DM Clinical Knowledge Summaries of the Clarity Informatics (UK). The feedback given by the Guideline Development Group on the draft version was used to amend and finalize the clinical guideline. Results: A clinical guideline for managing T2DM in adults by Ayurvedic practitioners was developed, which focuses on how practitioners can provide appropriate care, education, and support for people with T2DM (and their carers and family). The clinical guideline provides information on T2DM, such as its definition, risk factors, prevalence, prognosis, and complications; how it should be diagnosed and managed through lifestyle changes like diet and physical activity and Ayurvedic medicines; how the acute and chronic complications of T2DM should be detected and managed (including referral to specialists); and advice on topics like driving, work, and fasting including during religious/socio-cultural festivals. Conclusion: We systematically developed a clinical guideline for Ayurvedic practitioners to manage T2DM in adults.

A rapid HPTLC method to estimate piperine in Ayurvedic formulations.

BACKGROUND: Trikatu, Sitopaladi, Hingavastaka, Avipattikara, Sringyadi and Talisadya are very popular Ayurvedic (churna) medicines practiced in India; however, unfortunately, they possess several quality control issues. OBJECTIVE: The aim of this study was to find out a simple, accurate and sensitive HPTLC method for the detection and quantification of marker molecule, piperine (alkaloid) on these Ayurvedic formulations for standardization. MATERIALS AND METHODS: Methanolic extraction (reflux) was performed from the above six churnas as well as three single ingredients Piper longum (pipul), Piper nigrum (marich) and Piper chaba (chai). HPTLC was done using piperine as a standard. The mobile phase was a mixture of toluene-ethyl acetate (7:3, v/v) and detection at 342λ. RESULTS: The Rf was detected at 0.39. Piperine was quantified in all samples. P. nigrum showed higher piperine than P. longum and P. chaba. The maximum piperine was noted in Hingavastaka churna and followed by Sringyadi churna, Sitopaladi churna, Talisadya churna, Trikatu churna and Avipattikara churna. CONCLUSION: This method can be successfully employed for standardization and quantitative analysis of piperine in Ayurvedic formulations (churnas) and also be helpful to clinicians and pharmacists to draw significant role of piperine present in all these samples.

Effect of Coelogyne cristata Lindley in alleviation of chronic fatigue syndrome in aged Wistar rats.

BACKGROUND: Swarna Jibanti scientifically known as Coelogyne cristata Lindley (Orchidaceae), an orchid mentioned in Ayurvedic medicine is used to promote healthy life span. OBJECTIVE(S): The present work was planned to study the efficacy of hydro-alcoholic extract of pseudobulbs of C. cristata (CCE) to assess its role on chronic fatigue syndrome (CFS) induced behavioural and biochemical changes in aged Wistar rats compared to Panax ginseng (PG), a prototype anti-stress agent. MATERIALS AND METHODS: CFS was induced by forced swimming for consecutive 21 days for fixed duration (15 min sessions). The criteria of CFS due to fatigue were counted using locomotor activity, depression and anxiety through automated photactometer, immobility time and plus maze activity respectively. Acute toxicity study of CCE (upto 2 g/kg, Limit test) was also performed. For CFS, animals were divided into five groups, naive control, control, CCE treated (25 mg/kg b.w., 250 mg/kg b.w.) and standard PG treated (100 mg/kg b.w.) groups. All drugs were given orally for consecutive 21 days along with CFS. After assessing behavioural parameters, all animals were sacrificed at day 21 and in vivo antioxidant potential of CCE was determined by lipid peroxides, nitrite, catalase (CAT) and superoxide dismutase (SOD) in brain tissue. RESULTS: CCE was found to be non-toxic. CCE treated aged rats significantly improved (p < 0.001) the spontaneous locomotor movement with respect to control rats, while, decreased the mobility period or depression score. In CFS, CCE also enhanced the time spent (p < 0.001) in open arms while reducing the time spent in closed arm as compared to CFS control, indicating lowering anxiety score. Moreover, marked diminution in lipid peroxidation, nitrite and SOD level was exhibited after CCE treatment and significantly enhanced catalase level significantly (p < 0.01) with respect to CFS control. PG also showed similar actions. CONCLUSION: The results confirmed the potential therapeutic actions of CCE against experimentally induced CFS in aged rats that might be due to its CNS mediatory antioxidant properties.

A Comparative Study of Lipid-Lowering Effects of Guggul and Atorvastatin Monotherapy in Comparison to Their Combination in High Cholesterol Diet-Induced Hyperlipidemia in Rabbits.

BACKGROUND: Hypolipidemic activity of gugulipid has been widely described in traditional literature. OBJECTIVE: This study was done to evaluate hypolipidemic activity of guggul and atorvaststin monotherapy in comparison to their combination in rabbits. MATERIALS AND METHODS: Male New Zealand White rabbits (body weight 1.3-1.8 kg and age 8-10 weeks) were made hyperlipidemic by feeding cholesterol (0.5 g/kg) for three weeks and randomly divided into a control and three treatment groups receiving: atorvastatin (3.7 mg/kg), guggul (3.5 mg/kg) and their combination (same dose) for the next three weeks. Body weight measurements, estimation of serum lipid profile were done at the beginning, after three and six weeks, respectively. Histopathological examination of liver, heart and aorta was done after six weeks. Statistical analysis was done with SPSS version 16.0 using one-way and repeated measures analysis of variance (ANOVA) followed by post-hoc multiple comparison test with two tailed P value < 0.05 as significant. RESULTS: All treated groups had significant reduction in cholesterol, triglyceride, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) in comparison to pre-treatment values and control group, and had significant increase in high-density lipoprotein (HDL) in comparison to pre-treatment values. CONCLUSION: Combination of atorvastatin and guggul was comparable to their monotherapies in improving lipid profile.

The prevalence of dyslipidemia in patients with diabetes mellitus of ayurveda Hospital.

BACKGROUND: Dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus. Early detection and treatment of dyslipidemia in type-2 diabetes mellitus can prevent risk for atherogenic cardiovascular disorder. The rationale of this study was to detect the lipid abnormality in diabetic patients. METHODS: Necessary data was collected from the medical archives of 150 patients (73 female and 77 male) with diabetes mellitus registered in Department of pathology and biochemistry of a Ayurveda hospital established at Kolkata, India. RESULTS: The mean ages of female and male subjects were 51.8 ± 10.8 and 53.2 ± 11.3 years respectively. The range and mean value of FBS in females were 113-342 mg/dl and 157.7 ± 6.3 mg/dl, while the range and mean value of PPBS in females were 135-560 mg/dl and 275.5 ± 12.3 mg/dl respectively. Results showed that range and mean value of FBS in males were 111-462 mg/dl and 160.8 ± 7.4 mg/dl, while the range and mean value of PPBS in males were 136-598 mg/dl and 302.1 ± 12.6 mg/dl respectively. Results of serum lipids showed that the mean values for total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) in female patients were 202.2 ± 5.9 mg/dl, 168.3 ± 8.2 mg/dl, 44.9 ± 1.3 mg/dl, 123.6 ± 5.2 mg/dl and 33.7 ± 1.7 mg/dl respectively. The mean values for TC, TG, HDL-C, LDL-C and VLDL-C in male patients were 182.5 ± 4.8 mg/dl, 128.1 ± 10.8 mg/dl, 40.8 ± 1.2 mg/dl, 105.4 ± 4.8 mg/dl and 36.2 ± 2.2 respectively. FBS showed significant positive correlation with PPBS, cholesterol, TG, and VLDL-C. PPBS also demonstrated direct and significant correlations with TG and VLDL-C. CONCLUSIONS: The study showed common lipid abnormalities during diabetes induced dyslipidemia i.e., hypercholesterolemia, hypertriglyceridemia and elevated LDL-C. This study suggests the dominance of hyperlipidemia over increased prevalence of dyslipidemia.

Cytochrome P450 inhibitory potential and RP-HPLC standardization of trikatu--a Rasayana from Indian Ayurveda.

ETHNOPHARMACOLOGICAL RELEVANCE: Trikatu is a very well known 'Rasayana' in Ayurveda and widely used as a polyherbal ayurvedic formulation in India. It consists of three well known plants, viz., Piper longum (PL), Piper nigrum (PN) and Zingiber officinale (ZO) in equal ratio. Trikatu has been prescribed for cough, cold, fever, asthma, respiratory problems and improvement of digestive disorders. The aim of the present study was to investigate the effect of individual ingredients of trikatu namely PL, PN, and ZO and formulations [Marketed formulation (MF) and laboratory formulation (LF)] on drug metabolizing enzymes (CYP3A4 and CYP2D6), to assess its herb-drug interaction potential through cytochrome P450 inhibition assays. Further this work was aimed to develop an RP-HPLC method for the identification and quantification of piperine and 6-gingerol in the crude drug trikatu. MATERIALS AND METHODS: Enzyme inhibition effect of LF, MF, PL, PN and ZO was explored through CYP450-CO complex assay using rat liver microsomes (RLM) and a fluorescence screening method using individual isoenzymes (CYP3A4 and CYP2D6). The RP-HPLC method was developed for the identification and quantification of piperine and 6-gingerol in LF, MF and individual plant materials at the concentration of 1mg/mL. RESULTS: RP-HPLC analysis confirmed the presence of piperine and 6-gingerol in LF and MF [Piperine: 7.89±2.12% (w/w) (MF), 6.70±2.13% (w/w) (LF)]; [6-gingerol: 5.3±1.21% (w/w) (MF), 4.95±2.34% (w/w) (LF)]. Inhibitory potential of MF and LF in CYP450-CO complex assay was found to be 37.54±3.12% (MF) and 35.12±2.31% (LF) and against CYP2D6 and CYP3A4 was estimated to be IC50 251.30±3.98 and 245.23±1.92µg/mL and IC50 225.50±1.02 and 223.254±0.92µg/mL respectively. CONCLUSIONS: Different concentrations of the trikatu formulation and its individual components showed significantly (p<0.001) less inhibitory activity on individual isoenzymes as compared to the positive control. The crude drug exhibited inhibitory potential against the CYP450 enzymes in a concentration dependent manner. Outcome of the present study demonstrated that trikatu has less interaction potential with drug metabolizing enzymes.

Antidiabetic and antihyperlipidemic activity of hydroalcoholic extract of Withania coagulans Dunal dried fruit in experimental rat models.

OBJECTIVE: Evaluation of antidiabetic potential of the hydroalcoholic extract of Withania coagulans Dunal dried fruit (WCDF) alone and in combination with glipizide, in streptozotocin-induced diabetes, and evaluation of possible antihyperlipidemic activity of the same extract in high-cholesterol diet-induced hyperlipidemia, in albino rats. MATERIALS AND METHODS: Experimental diabetes was induced in 30 albino rats with intraperitoneal injection of streptozotocin (55 mg/kg). The rats were divided into five groups receiving the following treatments orally for 4 weeks: Vehicle, glipizide (2.5 mg/kg), WCDF extract (1000 mg/kg), WCDF extract (1000 mg/kg) plus glipizide (1 mg/kg) and WCDF extract (1000 mg/kg) plus glipizide (2.5 mg/kg). Fasting and postprandial blood glucose levels were measured every week for 4 weeks. Endocrine pancreas histopathology was done at the end. In a separate set of experiment, five groups of six albino rats each, received orally for 4 weeks, vehicle, cholesterol (25 mg/kg/day), cholesterol (25 mg/kg/day) plus atorvastatin (7.2 mg/kg/day), cholesterol (25 mg/kg/day) plus WCDF extract (1000 mg/kg/day) and no treatment, respectively. Estimation of serum lipid profile and liver histopathology was done at the end of 4 weeks. STATISTICAL ANALYSIS: Between-group and within-group comparisons were respectively done by analysis of variance (ANOVA) and repeated measures ANOVA, followed by post hoc Tukey's test, with a significance level of P < 0.05. RESULTS AND CONCLUSIONS: The 4-week treatment with WCDF extract significantly reversed hyperglycemia in streptozotocin-induced diabetes that was comparable to glipizide. When combined with glipizide (2.5 mg/kg), WCDF extract produced a synergistic antihyperglycemic effect as well as improvement in pancreatic histopathology. Moreover, hydroalcoholic extract of WCDF was effective and comparable to atorvastatin in controlling the high-cholesterol diet-induced hyperlipidemia in rats.

Adjunct therapy of Ayurvedic medicine with anti tubercular drugs on the therapeutic management of pulmonary tuberculosis.

BACKGROUND: Pulmonary tuberculosis (PTB) is an age old disease described in Vedic Medicine as 'Yakshma'. Later on, in Ayurveda it earned a prefix and found way into mythology as 'Rajayakshma'. After the discovery of streptomycin, the therapeutic management of PTB received a major breakthrough. The treatment module changed remarkably with the formulation of newer anti-tubercular drugs (ATD) with appreciable success. Recent resurgence of PTB in developed countries like United States posed a threat to the medical community due to resistant strains. Consequently, WHO looked toward traditional medicine. Literature reveals that Ayurvedic treatment of PTB was in vogue in India before the introduction of ATD with limited success. Records show that 2766 patients of PTB were treated with Ayurvedic drugs in a tertiary care hospital in Kolkata in the year 1933-1947. OBJECTIVES: To evaluate the toxicity reduction and early restoration by adjunct therapy of Ayurvedic drugs by increasing the bio-availability of ATDs. MATERIALS AND METHODS: In the present study, treatment response of 99 patients treated with ATD as an adjunct with Aswagandha (Withania somnifera) and a multi-herbal formulation described in Chikitsa-sthana of Charaka samhita i.e. Chyawanprash were investigated. Hematological profile, sputum bacterial load count, immunoglobulin IgA and IgM, blood sugar, liver function test, serum creatinine were the assessed parameters besides blood isoniazid and pyrazinamide, repeated after 28 days of treatment. RESULTS: The symptoms abated, body weight showed improvement, ESR values were normal, there was appreciable change in IgA and IgM patterns and significantly increased bioavailability of isoniazid and pyrazinamide were recorded. CONCLUSION: This innovative clinical study coupled with empowered research may turn out to be promising in finding a solution for the treatment of PTB.

Toxicological evaluation of Panchakola Avaleha, an Ayurvedic classical formulation, in albino rats.

The present study was carried out to assess the safety of standardized Panchakola Avaleha on albino rats (Wistar strain). Animals were administered three doses of Panchakola Avaleha by oral routes, viz. higher (500 mg/kg/day), middle (250 mg/kg/day), and therapeutic dose (50 mg/ kg/ day) for 28 consecutive days. Effects of the test drug on hematological, biochemical, and histopathologic parameters were evaluated. This study revealed normal behavior, no mortality, and no significant changes in hematological, biochemical, and histopathological examinations.