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1.
Clin Exp Dermatol ; 48(6): 617-622, 2023 Jun 05.
Article in English | MEDLINE | ID: mdl-36656771

ABSTRACT

BACKGROUND: Acne vulgaris is associated with insulin resistance and elevated insulin-like growth factor-1 (IGF-1). Metformin is commonly used for treatment of acne in patients with polycystic ovarian syndrome (PCOS). However, the benefits of metformin in patients with acne in general are not well established. AIM: To study the effectiveness of metformin treatment in patients with acne but who do not have PCOS and to understand the mechanisms of action of metformin in acne not related to PCOS. METHOD: In this observational study, 30 patients with clinically confirmed acne vulgaris were treated with metformin (1000 mg daily) for 3 months without any other topical or systemic active intervention for their acne. The effect of metformin at the clinical, hormonal and genetic level was assessed. RESULTS: Metformin monotherapy significantly (P < 0.001) decreased the global acne grading score for acne followed by a marginal increase in insulin; with a significant (P = 0.03) increase in insulin-like growth factor-1 (IGF-1). A significant (P < 0.001) decrease in free androgen index resulting from a significant (P < 0.001) increase in sex hormone-binding globulin (SHBG) with decrease in testosterone was observed. Homeostasis model assessment insulin resistance (HOMA-IR) was not significantly changed. Forkhead box protein O1 (FOXO1) expression was significantly (P = 0.006) downregulated with metformin treatment at the mRNA level without any significant changes at protein level. Expression of lipogenic genes, namely HMGCR, SQLE and ACSL5 (P = 0.001, P = 0.03, P = 0.03, respectively) were also downregulated. CONCLUSION: Metformin monotherapy led to significant clinical improvement in acne, possibly by reducing testosterone, inhibiting FOXO1 and reducing lipid synthesis by decreasing the expression of lipogenic genes.


Subject(s)
Acne Vulgaris , Insulin Resistance , Metformin , Polycystic Ovary Syndrome , Female , Humans , Metformin/pharmacology , Metformin/therapeutic use , Insulin-Like Growth Factor I , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/complications , Testosterone/therapeutic use , Insulin/therapeutic use , Acne Vulgaris/drug therapy , Acne Vulgaris/genetics , Acne Vulgaris/complications , Gene Expression , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use
2.
Dermatol Ther ; : e15449, 2022 Mar 14.
Article in English | MEDLINE | ID: mdl-35289044

ABSTRACT

BACKGROUND: The literature suggests a beneficial role of cholinomimetic agents in the treatment of pemphigus. In the present open-label, prospective pilot study, we assessed the effectiveness of topical pilocarpine 2% eye-drops in the treatment of recalcitrant oral lesions of pemphigus. METHODS: Twenty patients with recalcitrant oral lesions of pemphigus were recruited and instructed to apply pilocarpine 2% eye-drops twice daily on the resistant oral lesions for 180 days. The systemic immunosuppression at the time of inclusion in the present study was continued at the same dose throughout the study duration. The photographs of the lesions were obtained at baseline and an interval of 30 days. The area representing the erosion was measured on clinical photographs using the imageJ software (National Institute of Health). Visual analogue scale and oral health impact profile-14 questionnaire were used to assess the degree of subjective improvement. Anti-desmoglein 1 and 3, and anti-acetylcholine M3 receptor antibodies were measured both in serum and saliva; at baseline and at the completion of the study. RESULTS: Twenty patients were recruited in this pilot study. Mean total duration of illness was 3.4±1.3 years. The mean area of the erosions decreased significantly from 142.01±130.05 mm2 to 44.38±67.78 mm2 at study completion at 180 days (p 0.002, paired t-test). Repeated measures ANOVA demonstrated a significant trend in the reduction of the mean area of the erosions from baseline to day 180 (p 0.002). Mean VAS decreased significantly from 7.2±1.0 at baseline to 5.1±1.9 at day 180 (paired t-test, p 0.001). Mean OHIP-14 decreased significantly from 10.1±2.7 at baseline to 8.4±2.9 at day 180. No significant difference was observed between pre- and post-treatment levels of anti-desmoglein 1, anti-desmoglein 3, and anti-acetylcholine M3 receptor antibodies, in both serum and saliva. LIMITATIONS: The depth component in the erosions could not be measured. An orabase formulation could be used in future studies to facilitate retention of the medication at the site of application. CONCLUSION: Topical pilocarpine holds potential for the treatment of recalcitrant oral lesions of pemphigus vulgaris. It probably brings about re-epithelialization without imparting any immunomodulatory activity. This article is protected by copyright. All rights reserved.

3.
Exp Dermatol ; 30(7): 966-972, 2021 07.
Article in English | MEDLINE | ID: mdl-33847400

ABSTRACT

Evidence for the effectiveness of metformin in the treatment of acne is limited. To assess its efficacy, comedones were experimentally induced in young New Zealand rabbit ear using Isopropyl Myristate (IM) followed by metformin treatment (30 mg/kg bodyweight) for 60 days with continued IM application. In another group, to check whether metformin pre-treatment affects subsequent comedone development by IM, metformin was given for 14 days and then withdrawn (14 days) followed by comedone development with IM and metformin treatment. At different time points, dermatoscopic images of rabbit ear were taken for clinical assessment. Blood and biopsy samples were taken for hormonal assessment, histological examination and gene expression. Histologically confirmed acne model was developed in rabbit ear. Follicular size increased significantly (p = 0.0004 in both groups) upon IM application. Metformin significantly decreased comedones size as observed in dermatoscopic (p = 0.0003 in group I, p = 0.0190 in group II) and histological examination (p = 0.0313 in group I and II). However, size of comedones developed after metformin pretreatment was significantly (p < 0.0001) smaller. The lipid content of sebaceous glands decreased with metformin without any significant changes in the assessed hormones and genetic expression. Overall, metformin was found to be clinically effective in experimentally induced acne and can be used in humans.


Subject(s)
Acne Vulgaris/drug therapy , Disease Models, Animal , Metformin/therapeutic use , Animals , Outcome Assessment, Health Care , Rabbits
4.
Contact Dermatitis ; 80(6): 359-364, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30681730

ABSTRACT

BACKGROUND: There are no Indian studies on the association between filaggrin gene (FLG) mutations and any dermatosis, including hand eczema. OBJECTIVES: To determine the prevalence of FLG mutations in Indian hand eczema patients, and examine associations between such mutations and any aetiological type of hand eczema. MATERIALS AND METHODS: A total of 163 patients and 86 controls were included. Patients were categorized into aetiological subtypes of hand eczema. FLG polymorphisms (S2889X, 2282del4, R501X, and Q2417X) were determined in patients and controls, and correlated with subtypes. RESULTS: The prevalences of FLG mutations were 33.7% in cases and 3.5% in controls. Mutations in S2889X constituted 96.4% of all FLG mutations. No carrier of R501X and Q2417X mutations was identified. Among 55 patients with mutations, irritant contact dermatitis (ICD) with or without atopy was found in 22 patients, allergic contact dermatitis (ACD) with or without atopy was found in 12, and idiopathic hand eczema was found in 12. There was a significant association of FLG mutations with ICD with or without atopy, ACD without atopy, and idiopathic subtypes. FLG mutations were associated with more severe hand eczema. CONCLUSIONS: S2889X mutation is commoner in patients than in controls. FLG polymorphisms are associated with specific subtypes of hand eczema and severe disease.


Subject(s)
Dermatitis, Allergic Contact/genetics , Dermatitis, Atopic/genetics , Dermatitis, Irritant/genetics , Hand Dermatoses/genetics , Intermediate Filament Proteins/genetics , Mutation , Adult , Aged , Case-Control Studies , Female , Filaggrin Proteins , Humans , India , Male , Middle Aged , Polymorphism, Genetic , Prospective Studies , S100 Proteins , Young Adult
5.
J Am Acad Dermatol ; 75(4): 768-773, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27476104

ABSTRACT

BACKGROUND: Polymorphisms of the insulin-like growth factor (IGF)-1 gene consisting of variable cytosine adenosine repeats in the promoter region may directly influence the expression of IGF-1. OBJECTIVE: We sought to assess the role of IGF-1 gene polymorphisms in determination of plasma IGF-1 levels, acne, and its severity. METHODS: In this case-control study, 80 patients with acne vulgaris of 4 severity grades as per Global Acne Grading System and 80 age- and gender-matched control subjects without acne were studied. All the study subjects were without any disorder or a history of drug intake likely to affect IGF-1 level within a year before the study inclusion date. IGF-1 polymorphism was determined by polymerase chain reaction and plasma levels of IGF-1 by enzyme-linked immunosorbent assay. Acne severity was assessed by Global Acne Grading System. RESULTS: Mean plasma IGF-1 level in acne cases was significantly higher than in non-acne controls (P = .04). Plasma IGF-1 level positively correlated with severity of acne (P = .01). Individuals homozygous for the 192-base pair (bp) allele had 4.29 times odds risk (95% confidence interval 1.38-13.33) of having acne and a significantly higher mean level of IGF-1 compared with non-192/non-192 participants. Individuals homozygous for the 192-bp allele had 3.08 times odds risk (95% confidence interval 1.15- 8.31) of having higher severity grade of acne compared with non-192/non-192 participants. LIMITATIONS: A relatively small number of participants were studied. CONCLUSIONS: Plasma IGF-1 levels positively correlate with severity of acne. The 192/192 homozygotes had higher risk of acne and higher severity grade of acne. Functional studies showing the relationship between IGF-1 promoter level polymorphism and actual gene expression in skin are warranted.


Subject(s)
Acne Vulgaris/genetics , Genetic Predisposition to Disease , Insulin-Like Growth Factor I/genetics , Acne Vulgaris/diagnosis , Acne Vulgaris/epidemiology , Adult , Analysis of Variance , Biomarkers/metabolism , Case-Control Studies , Confidence Intervals , Enzyme-Linked Immunosorbent Assay , Female , Genotype , Humans , India , Insulin-Like Growth Factor I/metabolism , Male , Polymorphism, Genetic , Risk Assessment , Severity of Illness Index
6.
Indian Dermatol Online J ; 15(2): 252-254, 2024.
Article in English | MEDLINE | ID: mdl-38550809

ABSTRACT

Background: Nodulocystic acne is a severe type of acne that is known to improve after treatment with isotretinoin. Melnik has hypothesized a unifying concept on the mechanism of acne pathogenesis involving altered expression of Forkhead box O transcription factor (FoxO1) and role of isotretinoin in improving acne via modulating this pathway. Aim: To evaluate the pathway proposed by Melnik in acne pathogenesis by analysing the difference in the expression of FoxO1, peroxisome proliferator-activated receptor (PPARγ), and androgen receptor (AR) between acne patients and non-acne controls and the effect of treatment with isotretinoin on change in expression of these genes in acne patients. Results: The gene expression of FoxO1 was non significantly higher in acne patients as compared to controls. After treatment with isotretinoin, a significant decrease in FoxO1 expression in acne patients at mRNA (P = 0.05) level was observed. There was a significant decrease in grade 3 positivity of FoxO1 at protein level (P = 0.0009). A decrease in androgen receptor positivity (P = 0.055) at protein level was also observed. Conclusion: Reduction in FoxO1 expression appears to be an important mechanism of action of isotretinoin in acne.

7.
iScience ; 27(2): 108764, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38313048

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for metabolic diseases. The bidirectional interactions between liver and gut made dysbiotic gut microbiome one of the key risk factors for NAFLD. In this study, we reported an increased abundance of Collinsella aerofaciens in the gut of obese and NASH patients living in India. We isolated C. aerofaciens from the fecal samples of biopsy-proven NASH patients and observed that their genome is enriched with carbohydrate metabolism, fatty acid biosynthesis, and pro-inflammatory functions and have the potency to increase ethanol level in blood. An animal study indicated that mice supplemented with C. aerofaciens had increased levels of circulatory ethanol, high levels of hepatic hydroxyproline, triglyceride, and inflammation in the liver. The present findings indicate that perturbation in the gut microbiome composition is a key risk factor for NAFLD.

8.
PLoS One ; 18(12): e0295839, 2023.
Article in English | MEDLINE | ID: mdl-38127951

ABSTRACT

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a complex disease which is characterized by the deposition of fats in the hepatocytes. Further, it progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. The increasing prevalence of NAFLD urges to find the non-invasive predictive biomarkers. In this study, we sought to determine increased BMP8B levels as predictors for the progression of NAFLD. METHODS: In the present cross-sectional study, circulatory BMP8B levels were measured in healthy controls (n = 56), NAFL patients (n = 72) and NASH patients (n = 77) by using an ELISA kit. Human hepatic BMP8B mRNA expression was measured in the liver tissue of control and NASH patients. In addition, BMP8B expression was confirmed by immunohistochemistry analysis. Furthermore, hepatic BMP8B mRNA expression was measured in wild type (WT) mice, WT mice fed with choline deficient high fat diet (WT+CDHF), iNOS (inducible nitric oxide synthase) knockout (iNOS-/-) mice, iNOS-/- fed with CDHF diet (iNOS-/-+CDHF). RESULTS: Increased circulatory BMP8B levels and BMP8B mRNA expression in hepatic tissue were significantly higher in NASH patients as compared with the control subjects. BMP8B expression was increased parallel to the fibrosis score in the hepatic tissues of NASH patients. It was observed that increased BMP8B levels have shown a significant positive correlation between aspartate aminotransferase (r = 0.31, p = 0.005), alanine aminotransferase (r = 0.23, p = 0.045), APRI (r = 0.30, p = 0.009), and Fib-4 score (r = 0.25, p = 0.036) in NASH patients. BMP8B has maintained a significant association with NASH and shown high sensitivity (92.91%) and specificity (92.73%) in NASH patients. Furthermore, increased BMP8B mRNA expression levels were observed in iNOS-/-+CDHF mice. CONCLUSION: Our study findings confirmed that BMP8B increases with the severity of the disease and BMP8B shows potential as a non-invasive predictive biomarker to identify NAFLD progression. However, future studies should investigate circulatory BMP8B levels in a large number of patients and also its impact on liver during NAFLD progression.


Subject(s)
Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Animals , Humans , Mice , Biomarkers/metabolism , Bone Morphogenetic Proteins/metabolism , Cross-Sectional Studies , Liver/metabolism , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/complications , RNA, Messenger/metabolism
9.
Article in English | MEDLINE | ID: mdl-37285928

ABSTRACT

Diet-induced obesity mouse models are widely utilized to investigate the underlying mechanisms of dyslipidemia, glucose intolerance, insulin resistance, hepatic steatosis, and type 2 diabetes mellitus (T2DM), as well as for screening potential drug compounds. However, there is limited knowledge regarding specific signature lipids that accurately reflect dietary disorders. In this study, we aimed to identify key lipid signatures using LC/MS-based untargeted lipidomics in the plasma, liver, adipose tissue (AT), and skeletal muscle tissues (SKM) of male C57BL/6J mice that were fed chow, LFD, or obesogenic diets (HFD, HFHF, and HFCD) for a duration of 20 weeks. Furthermore, we conducted a comprehensive lipid analysis to assess similarities and differences with human lipid profiles. The mice fed obesogenic diets exhibited weight gain, glucose intolerance, elevated BMI, glucose and insulin levels, and a fatty liver, resembling characteristics of T2DM and obesity in humans. In total, we identified approximately 368 lipids in plasma, 433 in the liver, 493 in AT, and 624 in SKM. Glycerolipids displayed distinct patterns across the tissues, differing from human findings. However, changes in sphingolipids, phospholipids, and the expression of inflammatory and fibrotic genes showed similarities to reported human findings. Significantly modulated pathways in the obesogenic diet-fed groups included ceramide de novo synthesis, sphingolipid remodeling, and the carboxylesterase pathway, while lipoprotein-mediated pathways were minimally affected. This study provides a tissue-specific comparison of lipid composition, highlighting the usefulness of DIO models in preclinical research. However, caution is warranted when extrapolating findings from these models to dyslipidemia-associated pathologies and their complications in humans.


Subject(s)
Diabetes Mellitus, Type 2 , Dyslipidemias , Fatty Liver , Glucose Intolerance , Humans , Male , Mice , Animals , Glucose Intolerance/complications , Glucose Intolerance/prevention & control , Insulin , Diabetes Mellitus, Type 2/complications , Mice, Inbred C57BL , Obesity/metabolism , Diet , Fatty Liver/metabolism , Phospholipids/metabolism , Sphingolipids , Dyslipidemias/complications
10.
Heliyon ; 9(11): e22051, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38027691

ABSTRACT

We evaluated the effects of select herbal extracts (Tinospora cordifolia [TC], Tinospora cordifolia with Piper longum [TC + PL], Withania somnifera [WS], Glycyrrhiza glabra [GG], AYUSH-64 [AY-64], and Saroglitazar [S]) on various parameters in a diet-induced obesity mouse model. After 12 weeks of oral administration of the herbal extracts in high-fat diet (HFD)-fed C57BL/6J mice, we analyzed plasma biochemical parameters, insulin resistance (IR), liver histology, and the expression of inflammatory and fibrosis markers, along with hepatic lipidome. We also used a 3D hepatic spheroid model to assess their impact on profibrotic gene expression. Among the extracts, TC + PL showed a significant reduction in IR, liver weight, TNF-α, IL4, IL10 expression, and hepatic lipid levels (saturated triglycerides, ceramides, lysophosphocholines, acylcarnitines, diglycerides, and phosphatidylinositol levels). Saroglitazar reversed changes in body weight, IR, plasma triglycerides, glucose, insulin, and various hepatic lipid species (fatty acids, phospholipids, glycerophospholipids, sphingolipids, and triglycerides). With the exception of GG, Saroglitazar, and other extracts protected against palmitic acid-induced fibrosis marker gene expression in the 3D spheroids. TC + PL and Saroglitazar also effectively prevented HFD-induced insulin resistance, inflammation, and specific harmful lipid species in the liver.

11.
Mol Omics ; 19(10): 787-799, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-37534494

ABSTRACT

The present study evaluated the therapeutic potential of the medicinal plant Lysimachia candida Lindl. against metabolic syndrome in male SD rats fed with a high-fat high-fructose (HFHF) diet. Methanolic extract of Lysimachia candida Lindl. (250 mg kg-1 body weight p.o.) was administrated to the HFHF-fed rats daily for 20 weeks. Blood samples were collected, and blood glucose levels and relevant biochemical parameters were analysed and used for the assessment of metabolic disease phenotypes. In this study, Lysimachia candida decreased HFHF diet-induced phenotypes of metabolic syndrome, i.e., obesity, blood glucose level, hepatic triglycerides, free fatty acids, and insulin resistance. Liquid chromatography-mass spectrometry-based metabolomics was done to study the dynamics of metabolic changes in the serum during disease progression in the presence and absence of the treatment. Furthermore, multivariate data analysis approaches have been employed to identify metabolites responsible for disease progression. Lysimachia candida Lindl. plant extract restored the metabolites that are involved in the biosynthesis and degradation of amino acids, fatty acid metabolism and vitamin metabolism. Interestingly, the results depicted that the treatment with the plant extract restored the levels of acetylated amino acids and their derivatives, which are involved in the regulation of beta cell function, glucose homeostasis, insulin secretion, and metabolic syndrome phenotypes. Furthermore, we observed restoration in the levels of indole derivatives and N-acetylgalactosamine with the treatment, which indicates a cross-talk between the gut microbiome and the metabolic syndrome. Therefore, the present study revealed the potential mechanism of Lysimachia candida Lindl. extract to prevent metabolic syndrome in rats.


Subject(s)
Metabolic Syndrome , Rats , Animals , Metabolic Syndrome/drug therapy , Metabolic Syndrome/prevention & control , Blood Glucose/analysis , Blood Glucose/metabolism , Lysimachia , Fructose , Rats, Sprague-Dawley , Diet, High-Fat/adverse effects , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Phenotype , Amino Acids/metabolism , Disease Progression , Candida/metabolism
13.
Biomed Pharmacother ; 144: 112357, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34794234

ABSTRACT

Higher global prevalence of non-alcoholic fatty liver disease (NAFLD) is associated with obesity, steatosis, and insulin resistance (IR), and often progresses to steatohepatitis (NASH). Even after more than twenty years of research, there is still no FDA approved therapy for the treatment of fatty liver disease/NASH though, Saroglitazar - a dual PPAR α/γ agonist has been recently approved as a therapeutic option for the fatty liver disease in India. Hepatoprotective Ayurvedic formulations are widely used and are considered safe. In the present study, C57BL/6 male mice on HFHF diet for four weeks were treated with vehicle, Saroglitazar (3 mg/kg/po), and Hepano - a formulation of five herbs (200 mg/kg/po), at the human equivalent therapeutic doses for additional eight weeks. These animals were evaluated after 12 weeks for obesity, body mass index (BMI), systemic insulin resistance, hyperglycaemia, dyslipidaemia, and hepatic lipid accumulation. Differential liquid chromatography-mass spectrometry (LC-MS/MS) based lipidomics analysis demonstrated significant changes in the different class of lipids [phospholipids, sphingolipids, diglycerides and triglycerides (TG)] in HFHF fed group. The protective effects of both Saroglitazar and Hepano were evident against IR, obesity and in the modulation of different class of lipids in the circulation and hepatic tissue. Saroglitazar reduced TG as well as modulated phospholipids levels, while Hepano modulated only phospholipids, ceramides, oxidised lipids, and had no effect on hepatic or circulating TG levels in HFHF fed mice. In addition, in vitro studies using HepG2, THP1 and LX2 cells demonstrated safety of both the test substances where Hepano possess better anti-inflammatory as well as anti-fibrotic potential. Overall, Saroglitazar seems to be more efficacious than Hepano in the regimen used against HFHF induced IR, obesity, and dyslipidaemia.


Subject(s)
Diet, High-Fat , Fatty Liver/prevention & control , Fructose/adverse effects , Hypolipidemic Agents/therapeutic use , Insulin Resistance , Lipid Metabolism/drug effects , Liver/metabolism , Obesity/prevention & control , Phenylpropionates/therapeutic use , Pyrroles/therapeutic use , Animals , Cell Line , Diet , Fatty Liver/etiology , Humans , Lipidomics , Lipids/blood , Liver/drug effects , Male , Mice , Mice, Inbred C57BL , Obesity/etiology
14.
Front Pharmacol ; 12: 653872, 2021.
Article in English | MEDLINE | ID: mdl-33935766

ABSTRACT

Fatty liver is one of the most common metabolic syndrome affecting the global population. Presently, limited treatment modalities with symptomatic approach are available for alleviating fatty liver. Traditional and herbal treatment modalities have shown evidence to improve the disease pathology. In the present research work, evaluation of a selected medicinal plant Lysimachia candida Lindl. was carried out to investigate its beneficial effects on fatty liver disease in rats. Male Sprague Dawley (SD) rats were fed with high-fat high-fructose diet to induce fatty liver phenotypes. After induction for 15 weeks, methanolic extract of Lysimachia candida Lindl. (250 mg/kg b. w. p. o.) was administrated to the rats daily for the next 17 weeks. Blood samples were collected at different time points to analyze fasting blood glucose levels and relevant biochemical parameters important for the assessment of metabolic disease phenotypes. Liquid chromatography-mass spectrometry (LC-MS) based metabolomics was done to study the dynamics of metabolic changes in the serum during disease progression and how the medicinally important plant extract treatment reversed the metabolic diseases. Multivariate data analysis approaches have been employed to understand the metabolome changes and disease pathology. This study has identified the interplay of some metabolic pathways that alter the disease progression and their reversal after administration of the plant extract. Different group of metabolites mainly bile acids, fatty acids, carnitines, and their derivatives were found to be altered in the diseased rats. However, all the metabolites identified between control and disease groups are mainly related to lipid metabolism. The results depict that the treatment with the above-mentioned plant extract improves the regulation of aberrant lipid metabolism, and reverses the metabolic syndrome phenotype. Therefore, the present study reveals the potential mechanism of the herbal extract to prevent metabolic syndrome in rats.

15.
Phytomedicine ; 93: 153761, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34715512

ABSTRACT

BACKGROUND: Premna herbacea Roxb., a perennial herb is well documented for its therapeutic uses among the traditional health care-givers of Assam, India. Scientific validation on the traditional use of the medicinal plant using modern technology may promote further research in health care. PURPOSE: This study evaluates the therapeutic potential of methanolic extract of P. herbacea (MEPH) against type 2 diabetes mellitus (T2DM) and its phytochemical(s) in ameliorating insulin resistance (IR), thereby endorsing the plant bioactives as effective anti-hyperglycemic agents. METHODS: The anti-diabetic potential of the plant extract was explored both in L6 muscle cells and high fructose high fat diet (HF-HFD) fed male Sprague Dawley (SD) rats. Bioactivity guided fractionation and isolation procedure yielded Verbascoside and Isoverbascoside (ISOVER) as bioactive and major phytochemicals in P. herbacea. The bioenergetics profile of bioactive ISOVER and its anti-hyperglycemic potential was validated in vitro by XFe24 analyzer, glucose uptake assay and intracellular ROS generation by flourometer, FACS and confocal microscopy. The potential of ISOVER was also checked by screening various protein markers via immunoblotting. RESULTS: MEPH enhanced glucose uptake in FFA-induced insulin resistant (IR) L6 muscle cells and decreased elevated blood glucose levels in HF-HFD fed rats. Isoverbascoside (ISOVER) was identified as most bioactive phytochemical for the first time from the plant in the Premna genus. ISOVER activated the protein kinase B/AMP-activated protein kinase signaling cascades and enhanced glucose uptake in IR-L6 muscle cells. ISOVER decreased the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) and increased that of mammalian target of rapamycin (mTOR), thereby attenuating IR. However, molecular docking revealed that ISOVER increases insulin sensitivity by targeting the JNK1 kinase as a competitive inhibitor rather than mTOR. These findings were further supported by the bioenergetics profile of ISOVER. CONCLUSION: This study for the first time depicts the functional properties of ISOVER, derived from Premna herbacea, in ameliorating IR. The phytochemical significantly altered IR with enhanced glucose uptake and inhibition of ROS through JNK-AKT/mTOR signaling which may pave the way for further research in T2DM therapeutics.


Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Animals , Diabetes Mellitus, Type 2/drug therapy , Energy Metabolism , Glucose , Glucosides , Insulin/metabolism , Male , Molecular Docking Simulation , Muscle Cells/metabolism , Phenols , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , TOR Serine-Threonine Kinases/metabolism
16.
J Diabetes Res ; 2019: 4632491, 2019.
Article in English | MEDLINE | ID: mdl-31871947

ABSTRACT

Diabetes, a metabolic disorder characterized by elevated fasting blood glucose levels, affects nearly 8% of the world population and was predicted that it would be the top seven leading cause of death in the next ten years. The incidence of diabetes and its morbidity are increasing rapidly in developing countries due to lifestyle change and intake of high-calorie diet occurring with urbanization. Medicinal plants and their products have been proven to be effective, less expensive, and safe for the treatment and prevention of diabetes. Although several medicinal plants known for the antidiabetic property are reported in the ancient medical textbook, there is always a scope to identify and validate less explored medicinal plants that are still practiced regularly by local and tribal people since ancient times. Here, in the present article, we would like to review a less explored medicinal plant, Dillenia indica, which has promising effects in treating diabetes and other diabetic-associated complications. In spite of its wide use in the Northeast region of India as traditional medicine, there is only one clinical study where the antidiabetic potential of the fruit powder has been shown. Further well-designed animal and human studies are needed to confirm the role of Dillenia indica in diabetes and its associated complications.


Subject(s)
Diabetes Complications/drug therapy , Diabetes Mellitus/drug therapy , Dilleniaceae , Hypoglycemic Agents/therapeutic use , Phytotherapy , Plant Extracts/therapeutic use , Animals , Diabetes Complications/diagnosis , Diabetes Complications/epidemiology , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Humans , Hypoglycemic Agents/adverse effects , Plant Extracts/adverse effects , Treatment Outcome
17.
Indian Dermatol Online J ; 10(4): 426-430, 2019.
Article in English | MEDLINE | ID: mdl-31334063

ABSTRACT

BACKGROUND: Hair loss is one of the most commonly reported and psychologically distressing adverse effects of chemotherapeutic agents. Studies on its impact on psychosocial aspect of cancer patients are lacking at present. OBJECTIVE: To study the chemotherapeutic agents causing hair loss and its psychosocial implications in adults. MATERIALS AND METHODS: Observational study was done for a period of 1 year, wherein all cancer patients, more than 18 years of age who developed hair loss while on chemotherapy were assessed for type of malignancy, details of chemotherapy protocol, their knowledge about chemotherapeutic agents induced hair loss, and its impact on their social life and patterns of adjustment to deal with it. A prevalidated closed-ended questionnaire was used as a data collection tool. RESULTS: Out of 179 patients, 96 (53.6%) were males as against 80 (44.6%) females, and 49 (27.3%) patients were between 18 and 30 years of age. Carcinoma lung was the most common malignancy seen in 46 (25.6%) patients followed by rectosigmoid carcinoma in 41 (22.9%) patients. Combination of cyclophosphamide and doxorubicin was the most common combination resulting in hair loss in 49 (27.3%) cancer patients. A total of 101 (56.4%) patients felt that hair loss was the worst side effect of chemotherapy, while 29 (16.2%) had to continue because it was life-saving. A total of 129 (72%) patients said hair loss is affecting their social life; 37 (20.6%) patients were using hair accessories while 69 (38.5%) did not even attempt to hide hair loss as they were too occupied with fear of disease. CONCLUSION: Chemotherapy-induced hair loss is a common adverse effect in cancer patients undergoing treatment. A thorough counseling about it and methods to deal with it should be a part of management of the patients.

18.
Indian J Dermatol ; 64(5): 377-382, 2019.
Article in English | MEDLINE | ID: mdl-31543532

ABSTRACT

INTRODUCTION: The term "serodiscordant couples" refers to an intimate partnership in which one partner is human immunodeficiency virus (HIV) positive and the other HIV negative. They form a special population which are constantly at risk of acquiring infection, require safer sexual and reproductive options, and are in constant psychological and emotional distress. AIMS: To describe the social, sexual, and reproductive issues and their impact on serodiscordant couples. MATERIALS AND METHODS: A cross-sectional study was conducted on HIV-serodiscordant couples, admitted or attending our outpatient department, where the couples had not separated. A detailed interview of the partners on social, sexual, and reproductive issues was conducted and the data were endorsed in the pro forma. RESULTS: Sixty-four serodiscordant couples were included in the study. Sixty-two (96.8%) males were seropositive compared to 2 (3.1%) females. Sixty-one (95.3%) patients were married and 3 (4.6%) were unmarried. Thirty-six (56.2%) patients were between the age group of 21 and 35 years, 21 (32.8%) between 36 and 55 years, and 7 (10.9%) between 56 and 70 years. Sixty-two (96.8%) patients had a heterosexual orientation compared to 2 (3.1%) patients who were homosexual. Twenty-one (32.8%) patients had a history of sexual encounter outside the relation while 27 (42.1%) were not aware of the source of infection. Fifty-one (79.6%) patients were on antiretroviral therapy (ART) compared to 13 (20.3%) patients who were not on ART. Thirty-one (48.4%) patients admitted to have a constant strain in relation while 16 (25%) were practicing safe sex. Thirty-nine (60.9%) patients had fear of disease transmission while 26 (40.6%) had fear of pregnancy. Forty-nine (76.5%) patients had children at the time of detection while 15 (23.4%) had no issue. Forty-one (64%) patients expressed desire to have children as compared to 23 (35.9%). CONCLUSION: The unique requirements of serodiscordant couples in terms of providing them safer sexual and reproductive options to prevent the transmission of HIV to the seronegative partner or the child during pregnancy need to be addressed for better patient management.

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