Dietary Flaxseed and Flaxseed Oil Differentially Modulate Aspects of the Microbiota Gut-Brain Axis Following an Acute Lipopolysaccharide Challenge in Male C57Bl/6 Mice.

The microbiota gut-brain axis (mGBA) is an important contributor to mental health and neurological and mood disorders. Lipopolysaccharides (LPS) are endotoxins that are components of Gram-negative bacteria cell walls and have been widely shown to induce both systemic and neuro-inflammation. Flaxseed (Linum usitatissimum) is an oilseed rich in fibre, n3-poly-unsaturated fatty acid (alpha-linolenic acid (ALA)), and lignan, secoisolariciresinol diglucoside, which all can induce beneficial effects across varying aspects of the mGBA. The objective of this study was to determine the potential for dietary supplementation with flaxseed or flaxseed oil to attenuate LPS-induced inflammation through modulation of the mGBA. In this study, 72 5-week-old male C57Bl/6 mice were fed one of three isocaloric diets for 3 weeks: (1) AIN-93G basal diet (BD), (2) BD + 10% flaxseed (FS), or (3) BD + 4% FS oil (FO). Mice were then injected with LPS (1 mg/kg i.p) or saline (n = 12/group) and samples were collected 24 h post-injection. Dietary supplementation with FS, but not FO, partially attenuated LPS-induced systemic (serum TNF-α and IL-10) and neuro-inflammation (hippocampal and/or medial prefrontal cortex IL-10, TNF-α, IL-1ß mRNA expression), but had no effect on sickness and nest-building behaviours. FS-fed mice had enhanced fecal microbial diversity with increased relative abundance of beneficial microbial groups (i.e., Lachnospiraceae, Bifidobacterium, Coriobacteriaceae), reduced Akkermansia muciniphila, and increased production of short-chain fatty acids (SCFAs), which may play a role in its anti-inflammatory response. Overall, this study highlights the potential for flaxseed to attenuate LPS-induced inflammation, in part through modulation of the intestinal microbiota, an effect which may not be solely driven by its ALA-rich oil component.

Cucurbita pepo seeds improve peripheral neuropathy in diabetic rats by modulating the inflammation and oxidative stress in rats.

BACKGROUND: Cucurbita pepo (C. pepo) is cultivated and used traditionally as vegetable as well as medicine in different parts of the world. The aim of current study was to investigate the potential of C. pepo in attenuation of diabetic neuropathy via using streptozotocin (STZ)-induced diabetes model in male wistar rats. MATERIALS AND METHODS: Diabetic neuropathy was induced by administration of STZ; 65 mg/kg, i.p. and Nicotinamide (NAD; 230 mg/kg i.p.) and assessed by measuring thermal hyperalgesia, mechanical hyperalgesia and motor nerve conduction velocity (MNCV) in experimental animals. Treatment with different doses of (100, 200 and 400 mg/kg, p.o.) petroleum ether extract of C. pepo (CPE) and hydroethanolic extract of C. pepo (CHE) was started from the 60th day of STZ/NAD administration and continued upto 90th day. RESULTS: CPE and CHE significantly attenuated the behavioural changes including hyperalgesia, allodynia and MNCV linked to diabetic neuropathy. Moreover, the oxidative stress and level of TNF-α, TGF-ß and IL-1ß was found to be significantly attenuated in experimental animals. CONCLUSION: Thus C. pepo might ameliorate the progression of diabetic neuropathy via modulation of chronic hyperglycemia and therefore and have therapeutic potential for treatment of diabetic neuropathic pain.

Ameliorative effect of Cephalandra indica homeopathic preparation in STZ induced diabetic nephropathy rats.

BACKGROUND: Diabetic nephropathy (DN) is the foremost cause of morbidity and has become the most recurrent cause of end-stage renal disease among diabetic patients. Thus, agents having antidiabetic effect along with safety potential in the kidneys would have a higher remedial value. OBJECTIVE: The present study aimed to investigate possible protective effect of homeopathic preparation of Cephalandra indica Mother tincture, 6C and 30 C potencies on DN in Wistar rats. MATERIALS AND METHODS: DN was induced by intraperitoneal injection of STZ (60 mg/kg) 15 min after Nicotinamide (230 mg/kg, i.p.) administration. Rats were divided into six groups (n = 6). Group 1 and 2 was kept normal control and diabetic control respectively whereas Groups 3-5 consist of diabetic nephropathy rats treated with different doses of C. indica Mother tincture, 6C and 30 C potencies for 45 days. Glimepride (10 mg/kg) was used as standard. DN was assessed by determining serum glucose, urea, uric acid, creatinine level and tissue histological examination. Tissue antioxidant enzymes (SOD, GSH, LPO) level was measured to assess the oxidative stress. Also, the level of advanced glycation end products in kidney was determined. RESULTS: Mother tincture, 6C and 30 C potencies of C. indica produced significant attenuation in the biochemical parameters used to assess diabetic nephropathy. Moreover, oxidative stress and AGE's level in kidney was also found to be significantly reduced. CONCLUSION: We conclude that Mother tincture, 6C and 30 C potencies of C. indica confers protective effect against diabetic nephropathy via inhibition of Oxidative stress and AGE's.

Dillenia indica L. attenuates diabetic nephropathy via inhibition of advanced glycation end products accumulation in STZ-nicotinamide induced diabetic rats.

The present study was aimed to evaluate advanced glycation end products (AGEs) inhibitory activity of alcohol and hydro-alcohol extract (DAE and DHE) of Dillenia indica L. (Family: Dilleniaceae) and its potential in treatment of diabetic nephropathy by targeting markers of oxidative stress. D. indica was evaluated for its in vitro inhibitory activity against formation of AGEs by using bovine serum albumin. Diabetes was induced in male Wistar rats by streptozotocin (65 mg/kg i.p.) 15 min after nicotinamide (230 mg/kg, i.p.) administration. Diabetic rats were treated with different doses of extracts (100, 200 and 400 mg/kg) to analyze their nephroprotective effect. Tissue antioxidant enzymes level was measured along with the formation of AGEs in kidney to assess the effect of D. indica in ameliorating oxidative stress. D. indica showed significant inhibition of AGEs formation in vitro. D. indica produced significant attenuation in the glycemic status, renal parameter, lipid profile and level of antioxidant enzymes proving efficacy in diabetic nephropathy. Moreover, D. indica produced significant reduction in the formation of AGEs in kidneys. The present study concludes that D. indica as a possible therapeutic agent against diabetic nephropathy.

Effect of Kaempferol isolated from seeds of Eruca sativa on changes of pain sensitivity in Streptozotocin-induced diabetic neuropathy.

Generation of excessive reactive oxygen species (ROS) and advanced glycation end products (AGEs), and cellular apoptosis are implicated in the pathogenesis of diabetic neuropathy. Present study was aimed to explore the effect of Eruca sativa and Kaempferol (KP) on hyperalgesia (thermal and mechanical); tactile allodynia, motor nerve conduction velocity (MNCV) and oxidative-nitrosative stress in streptozotocin (STZ) induced experimental diabetes. Neuropathy developed in diabetic rats was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with excess formation of AGEs and ROS. Chronic treatment with E. sativa hydroalcoholic extract (EHA; 100, 200 and 400 mg/kg) and KP (5 and 10 mg/kg) for 30 days starting from the 60th day of STZ administration significantly ameliorated behavioral and biochemical changes linked to diabetic neuropathy. Present study suggested that EHA and KP corrected hyperglycemia and reversed the pain response partially in diabetic rats along via modulating oxidative and nitrosative stress along with reduction of AGEs formation in diabetic rats. Thus E. sativa might be beneficial in chronic diabetes, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain.

Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin-nicotinamide induced diabetic nephropathy.

The present study aimed to evaluate the effect of alcohol (PA) and hydroalcohol (PHA) extract of Paeonia emodi Royale roots in treatment of streptozotocin-nicotinamide induced diabetic nephropathy. Diabetes mellitus was induced in male Wistar rats by streptozotocin (65 mg/kg intraperitoneally) 15 minutes after nicotinamide (230 mg/kg, intraperitoneally) administration and diabetic nephropathy was assessed by measuring serum glucose, renal parameters (urea, uric acid, creatinine, and blood urea nitrogen level) and lipid profile. The rats were treated with different doses of extracts (100 mg/kg, 200 mg/kg, and 400 mg/kg) for 45 days. Oxidative stress was assessed by measuring tissue antioxidant enzymes level along with the formation of advanced glycation end-products (AGEs) in kidney. PA and PHA (400 mg/kg) produced significant attenuation in the serum glucose level (165.08 ± 3.353 mg/dL and 154.27 ± 2.209 mg/dL, respectively) as compared to control. Elevated renal parameters, lipid levels, tissue antioxidant enzymes and AGE formation were also restored in a dose-dependent manner. These findings suggest that by amelioration of oxidative stress and formation of AGEs, PA and PHA significantly inhibited the progression diabetic nephropathy in rats.

Chromane isolated from leaves of Dillenia indica improves the neuronal dysfunction in STZ-induced diabetic neuropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Indian traditional medicine, Dillenia indica L. has shown therapeutic efficacy in various diseases. Fruits and leaves of the plant possess anti-oxidant and anti-inflammatory properties. Reactive oxygen species, formation of advanced glycation end products (AGEs) and apoptosis are implicated in the pathogenesis of diabetic neuropathy. AIM OF THE STUDY: The aim of the present study was to explore the effect of D. indica and its isolate, chromane (CR), on thermal and mechanical hyperalgesia, allodynia, MNCV and oxidative-nitrosative stress in streptozotocin-induced experimental diabetes. MATERIAL AND METHODS: Diabetes was induced by intraperitoneal administration of Streptozotocin (STZ; 65mg/kg) for the development of diabetic neuropathy. Chronic treatment with DAE (100, 200 and 400mg/kg, p.o.) and CR (5 and 10mg/kg, p.o.) for 30 days was started from the 60th day of STZ administration. Development of neuropathy was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with increased formation of AGEs and reactive oxygen species. RESULTS: significantly attenuated behavioral and biochemical changes associated with diabetic neuropathy. Present study suggested that DAE and CR ameliorated hyperglycemia and diabetic neuropathic pain via modulation of oxidative-nitrosative stress and reduction in AGEs formation in the diabetic rats. CONCLUSION: Thus D. indica might be beneficial in chronic diabetics, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain.

Therapeutic effect of Linum usitatissimum L. in STZ-nicotinamide induced diabetic nephropathy via inhibition of AGE's and oxidative stress.

The present study was aimed to evaluate the potential of petroleum ether and hydro-alcoholic extract of Linum usitatissimum (FPE and FHE) in STZ-nicotinamide induced diabetic nephropathy. GC-MS analysis of FPE revealed the presence of different fatty acids, heterocyclic compounds etc. Moreover, chromatography of FHE isolated Secoisolariciresinol diglycoside. After 30 days of STZ-administration, 100, 200 and 400 mg/kg of FPE and FHE were administered for 45 days. FPE and FHE produced significant attenuation in the glycemic status, renal parameter, lipid profile and level of antioxidant enzymes proving efficacy in diabetic nephropathy. Moreover, FPE and FHE produced significant reduction in the formation of AGEs in kidney. The results indicated that via amelioration oxidative stress and formation of AGEs, FPE and FHE produced significant nephroprotective effect in STZ- induced diabetic nephropathy in rats.

Distinct Biomarkers for Early Diagnosis of Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the foremost causes of mortality in diabetic patients as a result of increased urinary albumin excretion (UAE) rate and compromised renal function. INTRODUCTION: Determination of increased excretion of albumin in urine chiefly attribute to the onset and progression of DN. However, due to certain limitations of albuminuria, the search for more sensitive, specific and reliable renal biomarkers is required for early prediction of DN. METHODS: Bibliographic investigation was made to scrutinize the data reporting relevant biomarkers associated with DN and may be used to predict the onset and progression of nephropathy. RESULT AND CONCLUSION: Optimization of biomarkers for a clinical situation requires a prospective validation in large numbers of patients with diabetic nephropathy and needs to be performed in different critically ill populations.

Renoprotective effect of Bacopa monnieri via inhibition of advanced glycation end products and oxidative stress in STZ-nicotinamide-induced diabetic nephropathy.

Hyperglycemia and oxidative stress are involved in the development of diabetic nephropathy (DN). This study was designed to evaluate the effect of alcohol and hydroalcohol extract of Bacopa monnieri and stigmasterol isolated from B. monnieri in the treatment of DN. Diabetes was induced in male wistar rats by streptozotocin (65 mg/kg i.p.) 15 min after nicotinamide (230 mg/kg, i.p.) administration. After 30 days, the rats were treated with different doses of extracts (100, 200, and 400 mg/kg) and stigmasterol (5 and 10 mg/kg) for 45 days to analyze their nephroprotective effect and produced significant attenuation in the serum glucose level, uric acid, creatinine, and lipid levels. Moreover, there is improvement in the level of superoxide dismutase (SOD), glutathione (GSH), and decrease in lipid peroxidation in terms of TBARS. The formation of AGEs in kidneys was also significantly reduced. These findings suggest that B. monnieri and its isolate (stigmasterol) might inhibit the progression of DN.

Attenuating Diabetes: What Really Works?

Diabetes mellitus is characterized by loss of glucose homeostasis; altered metabolism of glucose, proteins and lipids. Although a number of effective allopathic medicines are currently available for treatment and management of diabetes, but prevalence of side effects and higher cost poses a big challenge to the goal of pharmacotherapy. Herbs are mine of medicinal agents that are found to be efficacious, cost effective and safe in preventing diabetes and a number of plants have been used in management or treatment of diabetes. Modern pharmacopoeia has a healthy number of plant derived medicines and a large number of medicines from allopathic system are derived from the plant sources. This review aims to assess currently available preclinical and clinical knowledge of medicinal herbs intended for the management of diabetes and their mode of action.

Efficacy of holmium laser urethrotomy and intralesional injection of Santosh PGI tetra-inject (Triamcinolone, Mitomycin C, Hyaluronidase and N-acetyl cysteine) on the outcome of urethral strictures.

INTRODUCTION: To study the efficacy of holmium laser urethrotomy with intralesional injection of Santosh PGI tetra-inject (Triamcinolone, Mitomycin C, Hyaluronidase and N-acetyl cysteine) in the treatment of urethral strictures. MATERIAL AND METHODS: A total of 50 patients with symptomatic urethral stricture were evaluated by clinical history, physical examination, uroflowmetry and retrograde urethrogram preoperatively. All patients were treated with holmium laser urethrotomy, followed by injection of tetra-inject at the urethrotomy site. Tetra-inject was prepared by diluting acombination of 40 mg Triamcinolone, 2 mg Mitomycin, 3000 UHyaluronidase and 600 mg N-acetyl cysteine in 5-10 ml of saline, according to the stricture length. An indwelling 18 Fr silicone catheter was left in place for 7-10 days.All patients were followed-up for 6-18 months postoperatively by history, uroflowmetry, and if required, retrograde urethrogram and micturating urethrogram every 3 months. RESULTS: 41 (82%) patients had asuccessful outcome,whereas 9 (18%) had recurrences during a follow-up ranging from 6-18 months. In <1 cm length strictures, the success rate was 100%, while in 1-3 cm and >3 cm lengthsthe success rates were 81.2% and 66.7% respectively. This modality, thus, has an encouraging success rate, especially in those with short segment urethral strictures (<3 cm). CONCLUSIONS: Holmium laser urethrotomy with intralesional injection ofSantosh PGI tetra-inject (Triamcinolone, Mitomycin C, Hyaluronidase, N-acetyl cysteine) is a safe and effective minimally-invasive therapeutic modality for short segment urethral strictures.

Diabetic peripheral neuropathy: current perspective and future directions.

Diabetic neuropathy is a heterogeneous group of disorders with extremely complex pathophysiology and affects both somatic and autonomic components of the nervous system. Neuropathy is the most common chronic complication of diabetes mellitus. Metabolic disruptions in the peripheral nervous system, including altered protein kinase C activity, and increased polyol pathway activity in neurons and Schwann cells resulting from hyperglycemia plays a key role in the development of diabetic neuropathy. These pathways are related to the metabolic and/or redox state of the cell and are the major source of damage. Activation of these metabolic pathways leads to oxidative stress, which is a mediator of hyperglycemia induced cell injury and a unifying theme for all mechanisms of diabetic neuropathy. The therapeutic intervention of these metabolic pathways is capable of ameliorating diabetic neuropathy but therapeutics which target one particular mechanism may have a limited success. Available therapeutic approaches are based upon the agents that modulate pathogenetic mechanisms (glycemic control) and relieve the symptoms of diabetic neuropathy. This review emphasizes the pathogenesis, presently available therapeutic approaches and future directions for the management of diabetic neuropathy.

Management of diabetic complications: a chemical constituents based approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Long term hyperglycemia leads to development of complications associated with diabetes. Diabetic complications are now a global health problem without effective therapeutic approach. Hyperglycemia and oxidative stress are important components for the development of diabetic complications. Over the past few decades, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets and less toxic side effects. This review aims to assess the current available knowledge of medicinal herbs for attenuation and management of diabetic complications and their underlying mechanisms. MATERIAL AND METHODS: Bibliographic investigation was carried out by scrutinizing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases (SCOPUS, PUBMED, SCIELO, NISCAIR, Google Scholar) to retrieve available published literature. The inclusion criteria for the selection of plants were based upon all medicinal herbs and their active compounds with attributed potentials in relieving diabetic complications. Moreover, plants which have potential effect in ameliorating oxidative stress in diabetic animals have been included. RESULTS: Overall, 238 articles were reviewed for plant literature and out of the reviewed literature, 127 articles were selected for the study. Various medicinal plants/plant extracts containing flavonoids, alkaloids, phenolic compounds, terpenoids, saponins and phytosterol type chemical constituents were found to be effective in the management of diabetic complications. This effect might be attributed to amelioration of persistent hyperglycemia, oxidative stress and modulation of various metabolic pathways involved in the pathogenesis of diabetic complications. CONCLUSION: Screening chemical candidate from herbal medicine might be a promising approach for new drug discovery to treat the diabetic complications. There is still a dire need to explore the mechanism of action of various plant extracts and their toxicity profile and to determine their role in therapy of diabetic complications. Moreover, a perfect rodent model which completely mimics human diabetic complications should be developed.