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 clinical guideline-based management of type 2 diabetes by ayurvedic practitioners in Nepal: A feasibility cluster randomized controlled trial protocol.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a common chronic condition with significant health and socioeconomic consequences. In Nepal, T2DM is a common disease for which people consult ayurvedic (traditional medical system) practitioners and use ayurvedic medicines. Strong concerns remain about the suboptimal T2DM management of many patients by ayurvedic practitioners, and therefore, based on the best available scientific evidence, we have developed a clinical guideline for managing T2DM by ayurvedic practitioners. The research question to be addressed by a definitive cluster randomized controlled trial (RCT) is whether the introduction of a clinical guideline can improve the management of T2DM by ayurvedic practitioners in Nepal as compared to usual ayurvedic management (i.e., without any clinical guideline). In preparation for this future work, this current study aims to determine the feasibility of undertaking the definitive cluster RCT. METHODS: This is a 2-arm, feasibility cluster RCT with a blinded outcome assessment and a qualitative evaluation. The study is conducted in 12 public and private ayurveda centers in and outside the Kathmandu Valley in Nepal (1:1 intervention:control). Eligible participants should be new T2DM adult patients (i.e., treatment naïve) - the glycated hemoglobin level should be 6.5% or above but less than 9%. At least 120 participants (60/group) will be recruited and followed up for 6 months. Important parameters, needed to design the definitive trial, will be estimated, such as the standard deviation of the outcome measure (i.e., glycated hemoglobin level at 6-month follow-up), intraclass correlation coefficient, cluster size, recruitment, the time needed to recruit participants, follow-up, and adherence to the recommended ayurvedic medicine. Semi-structured qualitative interviews will be conducted with around 20 to 30 participants and all the participating ayurvedic practitioners to explore their experiences and perspectives of taking part in the study and of the intervention and a sample of eligible people declining to participate in the study to explore the reasons behind nonparticipation. DISCUSSION: We are now conducting a feasibility cluster RCT in Nepal to determine the feasibility of undertaking the definitive cluster trial. The first participant was recruited on 17 July 2022. If the feasibility is promising (such as recruitment, follow-up, and adherence to the recommended ayurvedic medicine), then the parameters estimated will be used to design the definitive cluster trial. Decisions over whether to modify the protocol will mainly be informed by the qualitative data.

Effectiveness and Safety of Ayurvedic Medicines in Type 2 Diabetes Mellitus Management: A Systematic Review and Meta-Analysis.

Introduction: Many Ayurvedic medicines have the potential for managing type 2 diabetes mellitus (T2DM), with previous systematic reviews demonstrating effectiveness and safety for specific Ayurvedic medicines. However, many of the reviews need updating and none provide a comprehensive summary of all the Ayurvedic medicines evaluated for managing T2DM. Objective: The objective of this systematic review was to evaluate and synthesize evidence on the effectiveness and safety of Ayurvedic medicines for managing T2DM. Inclusion criteria: Published and unpublished RCTs assessing the effectiveness and safety of Ayurvedic medicines for managing T2DM in adults. Methods: The JBI systematic review methodology was followed. A comprehensive search of sources (including 18 electronic databases) from inception to 16 January 2021 was made. No language restrictions were applied. Data synthesis was conducted using narrative synthesis and random effects meta-analyses, where appropriate. Pooled results are reported as mean differences (MD) with 95% confidence intervals (CI). Results: Out of 32,519 records identified from the searches, 219 articles were included in the systematic review representing 199 RCTs (21,191 participants) of 98 Ayurvedic medicines. Overall, in the studies reviewed the methodology was not adequately reported, resulting in poorer methodological quality scoring. Glycated hemoglobin (HbA1c) was reduced using Aegle marmelos (L.) Corrêa (MD -1.6%; 95% CI -3 to -0.3), Boswellia serrata Roxb. (-0.5; -0.7 to -0.4), Gynostemma pentaphyllum (Thunb.) Makino (-1; -1.5 to -0.6), Momordica charantia L. (-0.3; -0.4 to -0.1), Nigella sativa L. (-0.4; -0.6 to -0.1), Plantago ovata Forssk. (-0.9; -1.4 to -0.3), Tinospora cordifolia (Willd.) Hook.f. and Thomson (-0.5; -0.6 to -0.5), Trigonella foenum-graecum L. (-0.6; -0.9 to -0.4), and Urtica dioica L. (-1.3; -2.4 to -0.2) compared to control. Similarly, fasting blood glucose (FBG) was reduced by 4-56 mg/dl for a range of Ayurvedic medicines. Very few studies assessed health-related quality of life (HRQoL). Adverse events were not reported in many studies, and if reported, these were mostly none to mild and predominately related to the gastrointestinal tract. Conclusion: The current evidence suggests the benefit of a range of Ayurvedic medicines in improving glycemic control in T2DM patients. Given the limitations of the available evidence and to strengthen the evidence base, high-quality RCTs should be conducted and reported.

An Approach to Screen Genotoxic-Susceptible Diabetic Population of Various Prakriti Groups for Personalized Disease Management.

Background: Ayurveda classifies human populations into three predominant groups as Vata, Pitta, and Kapha based on their "Prakriti'. Any disturbance in the equilibrium of Prakriti can cause various diseases. Objectives: The aim of the study was to link genotoxic variation among the three Prakriti having type 2 diabetes. Design: Type 2 diabetic patients and healthy individuals belonging to three predominant Prakriti were selected through the Prakriti Questionnaire screening as per the guidelines of the CSIR-TRISUTRA unit modified for type 2 diabetes disease. Settings/Location: Sixty individuals from three predominant Prakriti, each consisting of 10 diabetic patients and 10 healthy individuals, were chosen. Subjects: Clinically diagnosed outdoor patients of JBRMCH suffering from type 2 diabetes for 5 years (fasting blood glucose >140 mg/dL; HbA1C > 7.0) and healthy individuals were the subjects for study. Inclusion Criteria: Age limit: 30-70 years, Sex: Both, Habitant: Participants residing in West Bengal for the last five generations, Religion: Unspecified, Social entity: Both urban and rural, Education: High school to college, Economic status: Lower middle to middle classes. Exclusion Criteria: Participants were nonsmokers and nonalcoholics. An individual having a medical history of long-term illness or dwandaja Prakriti type was excluded here. Outcome Measures: Reactive oxygen species (ROS) generation, blood DNA content, DNA damage, apoptosis of blood cells, and interaction of DNA with various carcinogens were observed. Results: The yield of ROS and total cell damage were significantly higher in the diabetic Vata (p < 0.001) group compared with other Prakriti Decreased DNA content and increased DNA damage were observed in type 2 diabetic patients who belonged to Vata (p < 0.01) Prakriti. DNA of Vata Prakriti was more prone to lead and arsenic. Conclusions: The diabetic Vata Prakriti is a genetically susceptible group as it has a tendency to get affected by increased DNA damage, which could help in creating personalized management of diabetes among individual Prakriti.

Effectiveness and safety of Ayurvedic medicines in type 2 diabetes mellitus management: a systematic review protocol.

OBJECTIVE: The objective of this review is to evaluate and synthesize evidence on the effectiveness and safety of Ayurvedic medicines for managing type 2 diabetes mellitus. INTRODUCTION: Several randomized controlled trials have been conducted to assess the effectiveness and safety of Ayurvedic medicines for managing type 2 diabetes. Systematic reviews have been conducted on this topic but need to be updated. The findings from this review will be used to develop a clinical guideline for managing type 2 diabetes by Ayurvedic practitioners in India. INCLUSION CRITERIA: Randomized controlled trials assessing the effectiveness and safety of Ayurvedic medicines for managing type 2 diabetes in adults will be included in this systematic review. METHODS: The authors will search for a wide range of sources to find both published and unpublished studies, including, but not limited to, MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), PsycINFO (Ovid), Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Allied and Complementary Medicine Database (Ovid). No language restrictions will be applied. The JBI systematic review methodology will be followed when conducting the review. Data synthesis will be conducted using narrative synthesis and meta-analyses, where appropriate. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42018118285.

Evaluation of Cynodon dactylon for wound healing activity.

BACKGROUND AND AIMS: Research in the field of wound healing is very recent. The concept of wound healing is changing from day to day. Ayurveda is the richest source of plant drugs for management of wounds and Cynodon dactylon L. is one such. The plant is used as hemostatic and wound healing agent from ethnopharmacological point of view. Aim of the present study is scientific validation of the plant for wound healing activity in detail. MATERIALS AND METHODS: Aqueous extract of the plant was prepared and phytochemical constituents were detected by HPLC analysis. Acute and dermatological toxicity study of the extract was performed. Pharmacological testing of 15% ointment (w/w) of the extract with respect to placebo control and standard comparator framycetin were done on full thickness punch wound in Wister rats and effects were evaluated based on parameters like wound contraction size (mm2), tensile strength (g); tissue DNA, RNA, protein, hydroxyproline and histological examination. The ointment was applied on selected clinical cases of chronic and complicated wounds and efficacy was evaluated on basis of scoring on granulation, epithelialization, vascularity as well as routine hematological investigations. RESULTS: Significant results (p<0.05) were observed both in pharmacological and clinical studies. CONCLUSION: The present research with aqueous extract of Cynodon dactylon explores its potential wound healing activity in animal model and subsequent feasibility in human subjects. Phenolic acids and flavonoids present in c. dactylon supports its wound healing property for its anti-oxidative activity that are responsible for collagenesis.

Pharmacological evaluation and chemical standardization of an ayurvedic formulation for wound healing activity.

Wound healing is a topic of substantial prominence in Ayurveda, the Indian traditional system of medicine. Test drug Kshatantak Malam (KM), otherwise named as Baharer Nani, is described in Ayurveda since a long time for wound healing activity but necessitates scientific base. The test drug was prepared in the form of natural ointment with the plants like Achyranthes aspera, Allium cepa, and Canabis sativa under the base of butter in a specialized form of preparation. Chemical standardization was made on the basis of the physical character, rancidity test, extractive value, thin-layer chromatography, and gas chromatography. An 8-mm-diameter full-thickness punch was produced in Wistar rats. The test drug was applied topically and compared with standard comparators like framycetin ointment and povidone iodine ointment. Effects were observed on the basis of physical parameters like wound contraction size (mm(2)), wound index, healing period (days), tensile strength (g) and biochemical parameters like tissue DNA (mg/g), RNA (mg/g), total protein (mg/g), hydroxyproline (mg/g), PAGE study, and histopathological observations. Significant results (P < .05) were observed with KM in the punch wound model on the basis of various physical, biochemical, and histopathological parameters. The drug was found to be safe in acute and chronic toxicity models in animals. Chemically it is enriched with fatty substances.

Spermatheca gland extract of snail (Telescopium telescopium) has wound healing potential: an experimental study in rabbits.

The effects of spermatheca gland extract of snail (Telescopium telescopium) to promote wound healing were studied in an animal model. The spermatheca gland extract of the snail was used as a topical medicament to treat experimentally created full thickness wounds in 12 rabbits (Oryctologous cuniculus). Wound healing was assessed on the basis of physical, histomorphological, and histochemical changes on days 0, 3, 7, and 14. Statistically significant differences were observed between the groups in all measured parameters. These exciting findings suggest that the data should be further tested in animal models to better understand the potential for wound healing in the spermatheca gland extract of the marine snail.

Turmeric (Curcuma longa) rhizome paste and honey show similar wound healing potential: a preclinical study in rabbits.

The potential efficacy of fresh turmeric (Curcuma longa) paste to heal wounds was tested in a preclinical study in an animal model. Turmeric paste was compared with honey as a topical medicament against a control on experimentally created full-thickness circular wounds in 18 rabbits (Oryctolagous cuniculus). Wound healing was assessed on the basis of physical, histomorphological, and histochemical parameters on treatment days 0, 3, 7, and 14. Only tensile strength was measured on day 14 of treatment. It was observed that the wound healing was statistically significantly faster (P < .01) in both treatment groups compared to the control group.

Antidiabetic activity of Caesalpinia bonducella F. in chronic type 2 diabetic model in Long-Evans rats and evaluation of insulin secretagogue property of its fractions on isolated islets.

Caesalpinia bonducella F., is a shrub widely distributed throughout the coastal region of India and is ethnically used by the tribal people of Andaman and Nicober Island as a remedy of symptoms of diabetes mellitus. This ethnic report prompted the detail investigation of hypoglycemic activity of Caesalpinia bonducella seeds, initially on physiological hyperglycemic model and then on type 1 and type 2 sub-acute diabetic animal models which has already been reported. Evaluation of different extracts from Caesalpinia bonducella in chronic type 2 diabetic model alongwith insulin secretagogue activity of five fractions isolated from the Caesalpinia bonducella seed kernel are presented in this paper. Both the aqueous and ethanolic extracts showed potent hypoglycemic activity in chronic type 2 diabetic model. Two fractions BM 169 and BM 170 B could increase secretion of insulin from isolated islets.

Wound healing potential of Pterocarpus santalinus linn: a pharmacological evaluation.

The need for new therapeutics for wound healing has encouraged the drive to examine the nature and value of plant products. Ayurveda, the Indian traditional system of medicine, mentions the values of medicinal plants for wound healing. One of these is Pterocarpus santalinus. This article describes a pharmacological study to evaluate its toxicity as well as wound-healing potential in animal studies. Powder made from the wood of the P. santalinus tree was used to make up an ointment in a petroleum jelly base. No toxic effects were observed in 72 hours. Studies were done on punch and burn wound models on normal and diabetic rats using the test ointment, untreated and vehicle controls, and standard therapy. Physical and biochemical measurements were made. The test ointment-treated wounds healed significantly faster. On healing, collagenesis and biochemical measurements yielded supportive data. These studies permit the conclusion that the P. santalinus ointment is safe and effective in treating acute wounds in animal models.

The clinical evaluation of Pterocarpus santalinus Linn. Ointment on lower extremity wounds--a preliminary report.

Pterocarpus santalinus is described in the Ayurveda for its wide spectrum of medicinal properties including wound healing. Previously the authors reported animal studies that demonstrated that an ointment made from the bark of this tree was effective without any toxic effects. They used the same ointment in 6 cases of lower extremity wounds. Healing was observed in all wounds. The study was not controlled, the findings are presented here as case studies. Further studies are planned to develop a wound healing ointment from a locally available and inexpensive plant.

Anti-inflammatory and anti-platelet aggregation activity of human placental extract.

AIM: To find the anti-inflammatory and anti-platelet aggregatory activity of human placental extract (HPE, Placentrex). METHODS: The HPE was studied for anti-inflammatory effect in Wistar rats on carrageenin, serotonin (5-HT), and prostaglandin E1 (PGE1) induced edema in acute model and cotton pellet induced granuloma on sub-acute model. Anti-platelet aggregation was studied against protection of adinosine diphosphate (ADP)-induced aggregation of human platelet through in vitro study. RESULTS: HPE showed positive results both in acute and sub-acute models of inflammation. Highly significant (P<0.01) results were obtained against 5-HT induced acute inflammation and cotton pellet induced sub-acute inflammation in comparison with standard (diclofenac sodium) and control (normal saline) drugs. The anti-inflammatory property of HPE in animal model was well supported with clinical study of platelet aggregation. There was highly significant (P<0.01) inhibition of platelet aggregation with HPE at different doses against ADP. CONCLUSION: Our data suggest that human placental extract may be useful in suppressing inflammation and platelet aggregation.

Plant medicines of Indian origin for wound healing activity: a review.

Research on wound healing drugs is a developing area in modern biomedical sciences. Scientists who are trying to develop newer drugs from natural resources are looking toward the Ayurveda, the Indian traditional system of medicine. Several drugs of plant, mineral, and animal origin are described in the Ayurveda for their wound healing properties under the term Vranaropaka. Most of these drugs are derived from plant origin. Some of these plants have been screened scientifically for the evaluation of their wound healing activity in different pharmacological models and patients, but the potential of most remains unexplored. In a few cases, active chemical constituents were identified. Some Ayurvedic medicinal plants, namely, Ficus bengalensis, Cynodon dactylon, Symplocos racemosa, Rubia cordifolia, Pterocarpus santalinus, Ficus racemosa, Glycyrrhiza glabra, Berberis aristata, Curcuma longa, Centella asiatica, Euphorbia nerifolia, and Aloe vera, were found to be effective in experimental models. This paper presents a limited review of plants used in Ayurvedic medicine.

Advanced studies on the hypoglycemic effect of Caesalpinia bonducella F. in type 1 and 2 diabetes in Long Evans rats.

Caesalpinia bonducella, widely distributed throughout the coastal region of India and used ethnically by the tribal people of India for controlling blood sugar was earlier reported by us to possess hypoglycemic activity in animal model. This prompted us to undertake a detail study with the aqueous and ethanolic extracts of the seeds of this plant in both type 1 and 2 diabetes mellitus in Long Evans rats. Significant blood sugar lowering effect (P < 0.05) of C. bonducella was observed in type 2 diabetic model. Special emphasis was given on the mechanistic study by gut absorption of glucose and liver glycogen.