Wound healing potential of Acacia catechu in streptozotocin-induced diabetic mice using in vivo and in silico approach.

Background and aim: Acacia catechu Wild. (Fabaceae) barks are traditionally used in the treatment of diabetes and wounds. Therefore, the objective of the present study was to evaluate the wound healing potential of the alcoholic extract of A. catechu (EAC) in streptozotocin-induced diabetic mice. Experimental procedures: EAC was first subjected to phytochemical estimations and standardization using (-) epicatechin as marker with the help of HPLC. Diabetes was induced in mice using streptozotocin and the wound healing potential of EAC was evaluated using excision and incision wound models on topical and oral treatment. Various biochemical parameters, in vivo antioxidants, cytokine profiling, VEGF, and histopathological examination were also performed. Further, molecular docking studies were performed using ligand (-) epicatechin on human inducible nitric oxide synthase. Results and conclusion: Phytochemically, EAC showed the presence of tannins, flavonoids, phenolic compounds, and saponins, while the content of (-) epicatechin was reported to be 7.81% w/w. The maximum healing of wounds (91.84 ± 1.10%) was observed in mice treated with a combination of both topical (10% gel) and oral (extract at 200 mg/kg) followed by topically and orally treated groups respectively after 14 days of treatment. These groups also showed significant restoration of altered biochemical parameters, antioxidant enzymes and cytokines. The molecular docking studies confirmed the role of (-) epicatechin in stabilizing the human inducible nitric oxide synthase with inhibitor showing binding energy of -8.31 kcal/mol. The present study confirmed the role of (-) epicatechin as a major marker in diabetic wound healing potential of A. catechu.

Ethnomedicinal importance of Patuletin in Medicine: Pharmacological Activities and Analytical Aspects.

BACKGROUND: Plant-derived bioactive molecules have been a major source of therapeutics for human and veterinarian purposes. Different traditional medicine system across the globe had relied on natural resources to meet their demand of healthcare. Still in modern world pharmaceutical industries look for phytochemicals to develop new drugs. The current review explores patuletin, a flavonoid for its diverse reported pharmacological activities along with its analytical techniques. METHODS: Scientific data published on patuletin was collected from Scopus, Science Direct, Pubmed, Google, and Google Scholar. The collected data were analyzed and arranged as per specific pharmacological activities performed using in-vitro or in-vivo methods. Analytical methods of patuletin have been presented next to pharmacological activities, Results: Available scientific literature indicates patuletin has anti-inflammatory, cytotoxic, genotoxic, hepatoprotective, antiproliferative, antiplatelet, antinociceptive, and antioxidant activity. In addition to these activities, its biological potential on breast cancer, rheumatoid arthritis, aldose reductase, and different types of microorganisms has been also presented in this work. Analytical data on patuletin signified the importance of patuletin for the standardization of herbal products and derived medicine. CONCLUSION: It may be concluded that patuletin with its diverse biological activities and readily available analytical methods, holds the potential to be translated into a new drug entity.

Traditional complementary and alternative medicine (TCAM) for diabetic foot ulcer management: A systematic review.

Diabetic Foot Ulcers (DFUs) are a devastating micro-vascular complication of diabetes with an increased prevalence and incidence and high rate of morbidity and mortality. Since antibiotics are frequently used to treat DFU, managing the condition has proven to be extremely challenging and may eventually lead to the development of antibiotic resistance. Scientists from around the world are working to develop an alternative solution to the problem of drug resistance by exploring complementary and alternative medicines that may be obtained from natural sources. Hence, the review aims to comprehensively report the information on the natural treatments and therapy used to manage DFU. All of the information described in the current study was gathered from electronic scientific resources, including Google Scholar, PubMed, Scopus, Science Direct, and Springer Link. Findings from the current review revealed the pre-clinical and clinical utility of 18 medicinal plants, 1 isolated compound, 7 polyherbal formulations including herbal creams, a few micronutrients including vitamins and minerals, insect products such as propolis, honey and, Maggot debridement therapy for the treatment and management of DFU. Natural therapies possess better efficacy, low cost, and shorter duration of treatment when compared with the conventional treatments; hence, all information made available about them is crucial to alter the direction of treatment. Furthermore, the data presented in this review are up to date on the potential efficacy of natural complementary medicines for alleviating DFU problems in in vitro and in vivo tests, as well as clinical studies.

Ethnological validation of Ashwagandha (Withania somnifera L. Dunal) ghrita as 'Vajikarana Rasayana': In-silico, in-vitro and in-vivoapproach.

ETHNOPHARMACOLOGICAL RELEVANCE: Processing cow ghee (clarified butterfat) with therapeutic herbs, i.e. ghrita, is recognized for augmenting the therapeutic efficacy of plant materials. Ashwagandha ghrita (AG) is an effective Ayurvedic formulation consisting of Indian ginseng, i.e., Withania somnifera (L.) Dunal, the main constituent used to treat infertility, weakness, gynaecological disorders, and general debility. OBJECTIVES: The present investigation was undertaken to corroborate the ethnopharmacological claim of AG as 'Vajikarana Rasayana' for its aphrodisiac potential using bioinformatics (in-silico) and experimental (in-vitro and in-vivo) approaches. METHODS: AG was formulated as per the methods reported in Ayurved sarsangraha. AG was further subjected to HPLC, GCMS analysis, and biological (acute toxicity and aphrodisiac) assessment per the standard procedures. Thirty-eight bioactives of Indian ginseng were subjected to computational studies (molecular docking and network pharmacology) to confirm the plausible mechanism. RESULTS: AG was found to be safe up to 2000 mg/kg body wt., and it showed dose-dependent upsurge (p < 0.01 and p < 0.05, wherever necessary) in mount and intromission frequency, genital grooming, and anogenital sniffing at 150 and 300 mg/kg body weight suggesting aphrodisiac activity. In-vitro studies demonstrated significant relaxation of the Corpus Cavernosal Smooth Muscle at all concentrations in a dose-dependent manner. Furthermore, the results of molecular modelling studies were in agreement with the biological activity and showed interaction with phosphodiesterase-5 as a possible target. CONCLUSION: AG exhibited an aphrodisiac effect and substantiated the traditional claim of Indian ginseng-based ghrita formulation as 'Vajikarana Rasayana'.

Effect of "Murcchana samskara" on therapeutic efficacy of BhallatakadiGhrita.

'Bhallatakadi Ghrita' (BG), comprising the plant extracts of Semecarpus anacardium L., Argemone mexicana L., Cocculus hirsutus L., and Woodfordia fruticosa K. 'Murcchana samskara' of ghee before any 'ghrita-paka' preparation evidenced the maximum acceptability for topical application. The current study dealt with the effect of the 'Murcchana' process on the therapeutic efficacy of BG. In the first step, 'Murcchita' ghee was prepared as per reference texts and then developed the 'Murcchita Bhallatakadi Ghrita' (M-BG), which was further assessed for wound healing activity using incision and excision wound animal models. 'Murcchanasamskara' altered the wound healing ability of M-BG (100% wound contraction on 15th post wounding day with 13.50 ± 0.22 days complete re-epithelization time and 562.33 ± 7.37 g breaking strength). The presence of antioxidants, polyphenols, flavonoids, and fatty acids (known for their potential wound healing properties) in M-BG could accelerate the wound contraction rate (P < 0.001). The present investigation has corroborated the Ayurvedic/traditional attribute of 'Murcchanasamskara' to augment the medicinal properties of the BG.

Bioactivity and In Silico Studies of Isoquinoline and Related Alkaloids as Promising Antiviral Agents: An Insight.

Viruses are widely recognized as the primary cause of infectious diseases around the world. The ongoing global pandemic due to the emergence of SARS-CoV-2 further added fuel to the fire. The development of therapeutics becomes very difficult as viruses can mutate their genome to become more complex and resistant. Medicinal plants and phytocompounds could be alternative options. Isoquinoline and their related alkaloids are naturally occurring compounds that interfere with multiple pathways including nuclear factor-κB, mitogen-activated protein kinase/extracellular-signal-regulated kinase, and inhibition of Ca2+-mediated fusion. These pathways play a crucial role in viral replication. Thus, the major goal of this study is to comprehend the function of various isoquinoline and related alkaloids in viral infections by examining their potential mechanisms of action, structure-activity relationships (SAR), in silico (particularly for SARS-CoV-2), in vitro and in vivo studies. The current advancements in isoquinoline and related alkaloids as discussed in the present review could facilitate an in-depth understanding of their role in the drug discovery process.

Evaluation of pancreatic regeneration activity of Tephrosia purpurea leaves in rats with streptozotocin-induced diabetes.

BACKGROUND AND AIM: Flavonoid rich plant Tephrosia purpurea (T. purpurea), commonly known as Sarpunkha has been used in traditional systems of medicine to treat diabetes mellitus. However, its effectiveness in promoting regeneration of pancreas in diabetes has not been investigated. Therefore, the present study was undertaken to evaluate pancreatic ß-cells regeneration, antioxidant and antihyperlipidemic potentials of T. purpurea leaves extract, its fractions and main constituent Rutin in diabetic rats. EXPERIMENTAL PROCEDURE: The leaves extract and its fractions were first screened for acute and sub-chronic antidiabetic activity in a dose range of 250-500 mg/kg orally. Further, fractions with potent antidiabetic activity were screened for pancreatic ß-cells regeneration activity using histopathological studies and morphometric analysis, which was followed by estimation of biochemical parameters. RESULTS AND CONCLUSION: The most significant antidiabetic, pancreatic regeneration and antihyperlipidemic activity was exhibited by n-butanol soluble fraction of ethanol extract at the dose level of 500 mg/kg. Histopathology revealed that treatment with this fraction improved the ß-cell granulation of islets and prevented the ß-cells damage which was further confirmed by morphometric analysis. Thus, the present study validated the traditional use of T. purpurea plant in the treatment of diabetes, which might be attributed to pancreatic ß-cells regeneration potential of its active constituent Rutin. TAXONOMY CLASSIFICATION BY EVISE: Traditional Medicine; Metabolic Disorder; Experimental Design; Cell Regeneration and Histopathology.

Computational assessment of saikosaponins as adjuvant treatment for COVID-19: molecular docking, dynamics, and network pharmacology analysis.

Saikosaponins are major biologically active triterpenoids, usually as glucosides, isolated from Traditional Chinese Medicines (TCM) such as Bupleurum spp., Heteromorpha spp., and Scrophularia scorodonia with their antiviral and immunomodulatory potential. This investigation presents molecular docking, molecular dynamics simulation, and free energy calculation studies of saikosaponins as adjuvant therapy in the treatment for COVID19. Molecular docking studies for 23 saikosaponins on the crystal structures of the extracellular domains of human lnterleukin-6 receptor (IL6), human Janus Kinase-3 (JAK3), and dehydrogenase domain of Cylindrospermum stagnale NADPH-oxidase 5 (NOX5) were performed, and selected protein-ligand complexes were subjected to 100 ns molecular dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-GBSA method. Molecular docking and molecular dynamics simulation studies revealed that IL6 in complex with Saikosaponin_U and Saikosaponin_V, JAK3 in complex with Saikosaponin_B4 and Saikosaponin_I, and NOX5 in complex with Saikosaponin_BK1 and Saikosaponin_C have good docking and molecular dynamics profiles. However, the Janus Kinase-3 is the best interacting partner for the saikosaponin compounds. The network pharmacology analysis suggests saikosaponins interact with the proteins CAT Gene CAT (Catalase) and Checkpoint kinase 1 (CHEK1); both of these enzymes play a major role in cell homeostasis and DNA damage during infection, suggesting a possible improvement in immune response toward COVID-19.

An in-silico evaluation of different Saikosaponins for their potency against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets.

The Public Health Emergency of International Concern declared the widespread outbreak of SARS-CoV-2 as a global pandemic emergency, which has resulted in 1,773,086 confirmed cases including 111,652 human deaths, as on 13 April 2020, as reported to World Health Organization. As of now, there are no vaccines or antiviral drugs declared to be officially useful against the infection. Saikosaponin is a group of oleanane derivatives reported in Chinese medicinal plants and are described for their anti-viral, anti-tumor, anti-inflammatory, anticonvulsant, antinephritis and hepatoprotective activities. They have also been known to have anti-coronaviral property by interfering the early stage of viral replication including absorption and penetration of the virus. Thus, the present study was undertaken to screen and evaluate the potency of different Saikosaponins against different sets of SARS-CoV-2 binding protein via computational molecular docking simulations. Docking was carried out on a Glide module of Schrodinger Maestro 2018-1 MM Share Version on NSP15 (PDB ID: 6W01) and Prefusion 2019-nCoV spike glycoprotein (PDB ID: 6VSB) from SARS-CoV-2. From the binding energy and interaction studies, the Saikosaponins U and V showed the best affinity towards both the proteins suggesting them to be future research molecule as they mark the desire interaction with NSP15, which is responsible for replication of RNA and also with 2019-nCoV spike glycoprotein which manage the connection with ACE2. [Formula: see text] Communicated by Ramaswamy H. Sarma.

Identification of bioactive compounds from Glycyrrhiza glabra as possible inhibitor of SARS-CoV-2 spike glycoprotein and non-structural protein-15: a pharmacoinformatics study.

At present, the world is facing a pandemic named as COVID-19, caused by SARS-CoV-2. Traditional Chinese medicine has recommended the use of liquorice (Glycyrrhiza species) in the treatment of infections caused by SARS-CoV-2. Therefore, the present investigation was carried out to identify the active molecule from the liquorice against different protein targets of COVID-19 using an in-silico approach. The molecular docking simulation study of 20 compounds along with two standard antiviral drugs (Lopinavir and Rivabirin) was carried out with the help of Autodock vina software using two protein targets from COVID-19 i.e. spike glycoprotein (PDB ID: 6VSB) and Non-structural Protein-15 (Nsp15) endoribonuclease (PDB ID: 6W01). From the observed binding energy and the binding interactions, glyasperin A showed high affinity towards Nsp15 endoribonuclease with uridine specificity, while glycyrrhizic acid was found to be best suited for the binding pocket of spike glycoprotein and also prohibited the entry of the virus into the host cell. Further, the dynamic behavior of the best-docked molecules inside the spike glycoprotein and Nsp15 endoribonuclease were explored through all-atoms molecular dynamics (MD) simulation study. Several parameters from the MD simulation have substantiated the stability of protein-ligand stability. The binding free energy of both glyasperin A and glycyrrhizic acid was calculated from the entire MD simulation trajectory through the MM-PBSA approach and found to high binding affinity towards the respective protein receptor cavity. Thus, glyasperin A and glycyrrhizic acid could be considered as the best molecule from liquorice, which could find useful against COVID-19. Communicated by Ramaswamy H. Sarma.

Potential Leads from Liquorice Against SARS-CoV-2 Main Protease using Molecular Docking Simulation Studies.

AIM AND OBJECTIVE: At present, the world is facing a global pandemic threat of SARSCoV- 2 or COVID-19 and to date, there are no clinically approved vaccines or antiviral drugs available for the treatment of coronavirus infections. Studies conducted in China recommended the use of liquorice (Glycyrrhiza species), an integral medicinal herb of traditional Chinese medicine, in the deactivation of COVID-19. Therefore, the present investigation was undertaken to identify the leads from the liquorice plant against COVID-19 using molecular docking simulation studies. MATERIALS AND METHODS: A set of reported bioactive compounds of liquorice were investigated for COVID-19 main protease (Mpro) inhibitory potential. The study was conducted on Autodock vina software using COVID-19 Mpro as a target protein having PDB ID: 6LU7. RESULTS: Out of the total 20 docked compounds, only six compounds showed the best affinity towards the protein target, which included glycyrrhizic acid, isoliquiritin apioside, glyasperin A, liquiritin, 1-methoxyphaseollidin and hedysarimcoumestan B. From the overall observation, glycyrrhizic acid followed by isoliquiritin apioside demonstrated the best affinity towards Mpro representing the binding energy of -8.6 and -7.9 Kcal/mol, respectively. Nevertheless, the other four compounds were also quite comparable with the later one. CONCLUSION: From the present investigation, we conclude that the compounds having oxane ring and chromenone ring substituted with hydroxyl 3-methylbut-2-enyl group could be the best alternative for the development of new leads from liquorice plant against COVID-19.

Sars-cov-2 host entry and replication inhibitors from Indian ginseng: an in-silico approach.

COVID-19 has ravaged the world and is the greatest of pandemics in modern human history, in the absence of treatment or vaccine, the mortality and morbidity rates are very high. The present investigation identifies potential leads from the plant Withania somnifera (Indian ginseng), a well-known antiviral, immunomodulatory, anti-inflammatory and a potent antioxidant plant, using molecular docking and dynamics studies. Two different protein targets of SARS-CoV-2 namely NSP15 endoribonuclease and receptor binding domain of prefusion spike protein from SARS-CoV-2 were targeted. Molecular docking studies suggested Withanoside X and Quercetin glucoside from W. somnifera have favorable interactions at the binding site of selected proteins, that is, 6W01 and 6M0J. The top-ranked phytochemicals from docking studies, subjected to 100 ns molecular dynamics (MD) suggested Withanoside X with the highest binding free energy (ΔGbind = -89.42 kcal/mol) as the most promising inhibitor. During MD studies, the molecule optimizes its conformation for better fitting with the receptor active site justifying the high binding affinity. Based on proven therapeutic, that is, immunomodulatory, antioxidant and anti-inflammatory roles and plausible potential against n-CoV-2 proteins, Indian ginseng could be one of the alternatives as an antiviral agent in the treatment of COVID 19. Communicated by Ramaswamy H. Sarma.

Development and evaluation of aphrodisiac potential of a classical ayurvedic formulation, 'Kaamdev ghrita' in rat model.

BACKGROUND: Ghee is widely considered as the Indian name for clarified butterfat and processing of ghee with therapeutic herbs i.e. ghrita is renowned for augmenting their medicinal properties. Kaamdev ghrita (also known as 'VajikaranaRasayana') is cow ghee based classical Ayurvedic formulation from the aphrodisiac category, which is used to ameliorate and potentiate sexual performance and also in the treatment of sexual dysfunctions, infertility, and premature ejaculation. OBJECTIVE: Present research work deals with the organoleptic, physicochemical, and biological assessment of Kaamdev ghrita for its aphrodisiac activity using in-vivo animal models. MATERIAL AND METHODS: Kaamdev ghrita was prepared using Indian cow's ghee as per standard Ayurvedic classical texts and subjected to organoleptic (color, odor, taste, texture, touch), physicochemical (acid value, peroxide value, iodine value, saponification value, unsaponifiable matter, extractive values, refractive index, and specific gravity) analyses as per the standard pharmacopeial procedures. The aphrodisiac potential of ghrita in rat model was evaluated by monitoring sexual behavioral performance using different parameters (mount frequency and latency, intromission frequency and latency, anogenital grooming and sniffing) at the dose of 150 and 300 mg/kg body weight. RESULTS: The physicochemical evaluation of Kaamdev ghrita showed higher acid value, iodine value, refractive index, and specific gravity whereas the lower saponification and peroxide value than the plain ghee. Kaamdev ghrita revealed the presence of flavonoids, alkaloids, saponins, sterols, terpenoids, coumarins, tannins, and showed remarkable antioxidant activity by in-vitro assays. It augmented the sexual performance in a dose-dependent manner as indicated by significant improvement (P < 0.05) in mount frequency and latency, intromission frequency and latency, anogenital grooming, and sniffing as compared to plain ghee treated control group. The present investigation has corroborated the ethnopharmacological claim of Kaamdevghrita for its aphrodisiac potential. CONCLUSION: Kaamdev ghrita exhibited aphrodisiac activity which may be attributed to the presence of antioxidant herbs present in it. It is the first scientific report on validation of the traditional claim of Kaamdev ghrita for its aphrodisiac potential.

Effect of ethanolic extract of Solanum virginianum Linn. on neuropathic pain using chronic constriction injury rat model and molecular docking studies.

The present research work was designed to examine the neuroprotective effect of ethanolic extract of Solanum virginianum Linn. (SV) in chronic construction injury (CCI) of sciatic nerve-induced neuropathic pain in rats. The extract was initially standardized by high-performance thin-layer chromatography using solasodine as a biomarker and was then subjected to assess the degree of mechanical allodynia, thermal allodynia, mechanical hyperalgesia, thermal hyperalgesia and biochemical evaluations. Administration of SV (100 and 200 mg/kg; p.o.) and pregabalin (10 mg/kg; p.o.) as a reference standard significantly debilitated hyperalgesia and allodynia and notably restored the altered antioxidant level and pro-inflammatory cytokine (IL-1ß and TNF-α) expression in a dose-dependent manner. Further, to appraise the mechanistic approach of solasodine, docking simulation studies were done on the 3D structure of the voltage-gated N-type calcium channel (Cav 2.2), R-type calcium channel (Cav 2.3) and sodium channel (Nav 1.7), and the results revealed that solasodine properly positioned into Phe 19, Leu 32, Met 51 and Met 71 (FLMM pocket) of Cav 2.2 and Cav 2.3 and being a competitor of Ca2+/N-lobe it may inactivate these calcium channels but did not bind into the desired binding pocket of Nav 1.7. Thus, the study confirmed the role of solasodine as a major biomarker for the observed neuroprotective nature of Solanum virginianum.

The antidiarrhoeal evaluation of Psidium guajava L. against enteropathogenic Escherichia coli induced infectious diarrhoea.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Psidium guajava L. (Myrtaceae), commonly used as an edible fruit is traditionally used worldwide in treatment of various gastrointestinal problems including diarrhoea. The leaves of the plant have also been evaluated for antidiarrhoeal activity in various chemical induced diarrhoea models. OBJECTIVE: The main objective of the present study was to evaluate the potency of P. guajava leaves and its major biomarker quercetin against enteropathogenic Escherichia coli (EPEC) induced infectious diarrhoea using preclinical and computational model. MATERIAL AND METHODS: P. guajava alcoholic leaf extract (PGE) was initially standardized using HPLC taking quercetin as a biomarker and was then subjected to antidiarrhoeal evaluation on rats in an EPEC induced diarrhoea rat model. The study included assessment of various behavioral parameters, initially for 6 h and then for up to 24 h of induction which was followed by estimation of stool water content, density of EPEC in stools and blood parameters evaluation. The colonic and small intestinal tissues of the treated animals were subjected to various biochemical estimations, in vivo antioxidant evaluation, estimation of ion concentration, Na+/K+-ATPase activity, assessment of pro-inflammatory cytokines and histopathological studies. Further, the major biomarker off PGE, quercetin was subjected to molecular docking studies with Na+/K+-ATPase and EPEC. RESULTS: The results demonstrated a significant antidiarrhoeal activity of quercetin (50 mg/kg), PGE at 200 and 400 mg/kg, p.o., where quercetin and PFGE at 200 mg/kg, p.o. were found to be more prominent, as confirmed through higher % protection, water content of stools and density of EPEC in stools. PGE and its biomarker quercetin also significantly recovered the WBC, Hb, platelets loss and also revealed a significant restoration of altered antioxidants level, pro-inflammatory cytokines (IL-1ß and TNF-α) expression and had positive influence on Na+/K+-ATPase activity. The docking studies of quercetin with Na+/K+-ATPase showed favourable interactions and residues Glu 327, Ser 775, Asn 776, Glu 779 and Asp 804 of Na+/K+-ATPase were adequately similar to quercetin for donating ligands for binding, while quercetin was also found to terminate the linkage between mammalian cells and EPEC thus, preventing further infection from EPEC. CONCLUSION: Inhibition in intestinal secretion, reduced nitric oxide production and inflammatory expression along with reactivation of Na+/K-ATPase activity could be attributed to the observed antidiarrhoeal potential of PGE against infectious diarrhoea, where quercetin was confirmed to be the main contributing factor.

Quercetin a major biomarker of Psidium guajava L. inhibits SepA protease activity of Shigella flexneri in treatment of infectious diarrhoea.

The leaves of the plant Psidium guajava L. (Myrtaceae) has been traditionally used in treatment of various gastrointestinal disorders including diarrhoea and have also been reported for its potent antidiarrhoeal activity on various chemical induced diarrhoea models. The objective of our present study was to evaluate the potency of the leaf extract of the plant Psidium guajava (PGE) along with its major biomarker quercetin against Shigella flexneri-induced sub chronic model of infectious diarrhoea. PGE at 100, 200 and 400 mg/kg, p.o. and quercetin at 50 mg/kg, p.o. were administered to Shigella flexneri-induced diarrhoeal rats for five days and various behavioural parameters were evaluated on 1st, 3rd and 5th day of treatment. This was followed by assessment of stool water content, density of Shigella flexneri in stools and blood parameters examination. After treatment, colon and small intestine of rats was dissected and subjected to biochemical estimations, cytokine profiling, antioxidant evaluations, ion concentration determination, Na+/K+-ATPase activity and histopathology. Molecular docking studies on crystal structure of Secreted Extracellular Protein A (SepA) from Shigella flexneri with biomarker quercetin was also performed. PGE at 200 mg/kg followed by quercetin depicted maximum antidiarrhoeal potential, which was confirmed through diarrhoea score and % protection, while PGE at 400 mg/kg showed similar effect to PGE 200 mg/kg thus, the later may have ceiling effect. PGE and quercetin also significantly reduced the density of Shigella flexneri in stools, water content of stools and restored the alterations observed in blood parameters, antioxidant status and pro-inflammatory cytokines (IL-6 and TNF-α) expression. These parameters contributed in normalization of electrolyte balance, reactivation of Na+/K+-ATPase activity and repairing of epithelial tissue damage, confirmed through histopathology. Docking simulation studies revealed the role of quercetin in inactivating the protease activity of SepA, a protein secreted by Shigella, which disrupts epithelial barrier integrity during infection and also manages its signal production. Thus, the overall results confirmed the role of quercetin as a major biomarker for the observed antidiarrhoeal potential of P. guajava against Shigella flexneri induced infectious diarrhoea.

The potency of eriosematin E from Eriosema chinense Vogel. against enteropathogenic Escherichia coli induced diarrhoea using preclinical and molecular docking studies.

The main objective of the present study was to evaluate the potential of eriosematin E (ECM) isolated from the roots of Eriosema chinense against enteropathogenic Escherichia coli (EPEC) induced diarrhoea. ECM isolated from the bioactive chloroform fraction of E. chinense was subjected to antidiarrhoeal evaluation on rats against diarrhoea, induced by the oral suspension of EPEC. The study included evaluation of behavioral parameters for 6 h and up to 24 h of induction, followed by estimation of water content, the density of EPEC in stools and evaluation of various blood parameters. Further, the colonic and small intestinal tissues were subjected to biochemical estimations, antioxidant evaluation, determination of ion concentration, Na+/K+ -ATPase activity, pro-inflammatory cytokines assessment and histopathology. Finally, the impact of ECM on Na+/K+-ATPase was studied through molecular docking studies. Significant antidiarrhoeal potential of ECM was demonstrated at 5 and 10 mg/kg, p.o., however, ECM at 10 mg/kg, p.o. was found to be more effective, as confirmed through higher % protection, density of EPEC in stools and water content of stools. ECM also significantly increased the level of WBC, Hb, platelets and revealed restoration of altered antioxidants, pro-inflammatory cytokines (IL-1ß and TNF-α) status and also reactivated the suppressed Na+/K+-ATPase activity, which was also confirmed through docking studies showing H-bonding of hydroxyl group of ECM with amino acids Asp 190, Asn 167 and Glu 169 thus, maintaining proper electrolyte balance and also prevented epithelial tissue damage. The overall effect of ECM may be attributed to the decline in the elevated level of cytokines, inhibition in nitric oxide production and reactivation of Na+/K+-ATPase activity resulting in reduced intestinal secretion.

Wound healing potential of Solanum xanthocarpum in streptozotocin-induced diabetic rats.

OBJECTIVES: The objective of the present study was to evaluate wound healing potential of Solanum xanthocarpum extract in streptozotocin-induced diabetic rats. METHODS: Alcoholic extract of the aerial parts (ESX) was subjected to phytochemical estimations and its standardization with chlorogenic acid using HPLC. ESX was then evaluated for wound healing potential in, streptozotocin-induced diabetic rats using excision and incision wound models on topical and oral treatment Various biochemical evaluations, such as collagen, hexosamine, hyaluronic acid, protein, DNA along with antioxidant parameters, proinflammatory cytokines, VEGF and histopathological examination were also evaluated. KEY FINDINGS: Extract of S. xanthocarpum depicted the presence of mainly alkaloids, polyphenols, steroids, while content of chlorogenic acid was found to be 8.44% w/w. The maximum effective nature of ESX in healing was observed at 10% gel (topical) and 200 mg/kg (orally) in diabetic rats, where highest healing power was observed when treated both orally and topically. Biochemical evaluations showed significant increase in the levels of collagen, hexosamine, hyaluronic acid, protein, DNA followed by significant decline in the levels of blood glucose, lipid peroxidation, nitric oxide and expression of proinflammatory cytokines, supported by histopathology. CONCLUSIONS: The potential healing effect in diabetic rats may be attributed to the presence of chlorogenic acid in combination with other phytoconstituents.

Antidiarrhoeal activity of eriosematin E isolated from the roots of Eriosema chinense Vogel.

BACKGROUND: Roots of the plant Eriosema chinense Vogel (Fabaceae) is distributed mainly over the Eastern Himalayan region of India and China. The roots of the plant are used as a vegetable by the people of Northern Australia, China and North East India and are used traditionally by the tribal people of Meghalaya (India) for the treatment of diarrhoea. It has been reported to have significant antidiarrhoeal, cytotoxic and antimycobacterial activity. PURPOSE/OBJECTIVE: The present investigation was undertaken to isolate a lead molecule responsible for the observed antidiarrhoeal activity. METHODS: Eriosematin E, a prenylated flavanone, was isolated using column chromatography and was characterized by comparing its melting point and spectroscopic data (UV, IR, 1H NMR, 13C NMR, Mass Spectra) from literature. Eriosematin E (2.5, 5 and 10mg/kg p.o.) was then screened for normal faecal excretion rate and castor oil-induced diarrhoea models in rats. Further, it was examined for small intestinal transit, intestinal fluid accumulation and PGE2 induced enteropooling models in rats. Biochemical estimations and Na+ and K+ concentration in intestinal fluid were also determined along with colonic histopathological studies. RESULTS: The results illustrated a significant (P< 0.05) reduction in normal faecal output at 10mg/kg p.o. after 5th and 7thh of treatment and also showed maximum protection of 69.43% from diarrhoea in the castor oil-induced diarrhoea model. Significant results were also observed at the maximum effective dose of eriosematin E (10mg/kg p.o.) in inhibiting peristaltic index (small intestinal transit) and reducing intestinal fluid volume of castor oil induced and PGE2 induced enteropooling models. Further, eriosematin E restored all the alterations in biochemical parameters such as nitric oxide, protein, DNA, superoxide dismutase, catalase and lipid peroxidation. It also significantly recovered Na+ and K+ loss from body and confirmed its protective nature through the histopathological studies. CONCLUSION: The study corroborates the antidiarrhoeal potential of eriosematin E which may be attributed to its antisecretory and antioxidant potential.