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Kukkupuni, S. K.

Publications and source records attributed to Kukkupuni, S. K..

5 recordsLinked to original sources

Patolakaturohiniyadi Kashayam, exerts anti-steatotic and anti-obesogenic effects via coordinated regulation of lipid metabolism, inflammation, and incretin signalling.

BackgroundMetabolic dysfunction is characterized by dysregulated lipid metabolism, lipotoxicity, insulin resistance, and chronic low-grade inflammation, contributing to obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Multi-target therapeutic strategies that restore lipid homeostasis are of growing interest. Patolakaturohiniyadi Kashayam (PKR), a classical Ayurvedic polyherbal formulation, was investigated for its potential to modulate lipid metabolism and ameliorate metabolic dysfunction. MethodsAn integrated approach combining network pharmacology, in vitro, lipidomics, and in vivo studies was employed. Hub gene identification and KEGG pathway enrichment were performed to elucidate molecular targets. Anti-steatotic and anti-adipogenic effects were assessed in hepatocytes and adipocytes, followed by lipidomic profiling. Efficacy was further evaluated in a high-fat high-fructose diet (HFHFD)-induced animal model. ResultsNetwork pharmacology identified key targets including TP53, AKT1, IL6, TNF, and STAT3, enriched in pathways related to lipid metabolism, inflammation, and metabolic regulation. PKR significantly reduced lipid droplet accumulation and intracellular triglyceride levels in vitro. Lipidomics revealed suppression of diacylglycerol-mediated lipotoxicity and restoration of phospholipid balance, characterized by increased lysophospholipids and phosphatidylethanolamines with normalization of phosphatidylcholine species. In vivo, PKR reduced body, liver, and adipose tissue weights, improved serum lipid profiles, and decreased AST and ALT levels. Histological analyses demonstrated reduced lipid accumulation and inflammation, along with preservation of adipose tissue architecture. PKR also improved glucose tolerance and significantly elevated plasma GLP-1 levels. ConclusionPKR exerts potent anti-steatotic and anti-obesogenic effects through coordinated regulation of lipid metabolism, inflammation, and incretin signalling, highlighting its potential as a multi-target therapeutics for metabolic dysfunction.

pharmacology and toxicology↗

Punarnavayolepa Choornam in Iron Deficiency Anaemia management: Pharmaceutic insights and biological activity.

Background and AimIndigenous medical systems employ unique pharmaceutical techniques to meet the therapeutic needs. In the Indian System of Medicine, Ayurveda, a unique method called "Ayolepam" is described that facilitates efficient iron absorption from its source to the formulation. Punarnavayolepa Choornam (PC), prepared from Boerhavia diffusa L., is one such novel Ayolepam formulation developed by a traditional Ayurveda school of South India, widely used in the clinical management of iron deficiency anaemia. This study aims at scientifically evaluating the Ayolepam technique by assessing the iron binding and bioavailability properties of PC, prepared from the leaves, root and whole plant of B. diffusa, using in-vitro model systems.. Experimental ProcedureThe iron content in both raw and processed samples of PC was quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). A simulated in-vitro digestion model employed to assess the release of bioavailable iron from the formulation. Subsequently, iron bioavailability was evaluated using the Caco-2 cell model of human intestinal epithelium following the ferrozine method. Results and ConclusionPC preparation from leaves, whole plant and roots of B. diffusa, showed significant increase in iron content compared to the raw material. In-vitro digestion studies confirmed the efficient release of bioavailable iron from these formulations, and subsequent Caco-2 cell assays confirmed their iron bioavailability properties. In conclusion, these findings provide a preliminary scientific basis for this novel and unique pharmaceutical design from a traditional school of Ayurveda, supporting its clinical application.

pharmacology and toxicology↗

Genome Sequencing, Molecular Marker Development and Genetic Diversity Assessment of Economically Important Vulnerable Tree Species Saraca asoca (Roxb.) W.J de Wilde

Saraca asoca, is an understory tree along streams in evergreen to semi-evergreen forests up to 600 m. It is an important tree in cultural tradition and medicinally significant. It is native to India and Sri Lanka. Globally the species is found to occur in India, Sri Lanka, Myanmar, Bangladesh. It was introduced in Malaysia. Within India, its found in Western Ghat and Eastern Ghat. It is occasionally planted in gardens. Saraca asoca is known for its extensive pharmacological properties, particularly its bark is used in treating menorrhagia, dysfunctional uterine bleeding, hemorrhagic dysentery, and other gynecological issues, it holds a prominent place in Ayurvedic medicine. This study was undertaken to sequence the whole genome of Saraca asoca using the Illumina HiSeq2500 platform, and evaluating the genetic diversity among samples from Kolluru and other locations in southern India through Genotyping by Sequencing (GBS). Analysis of 49 samples established genetic diversity relationships using a distance matrix. Sequencing yielded 1.6 Gb, covering 76% of the estimated genome size. The genome includes 764 million bases of repetitive DNA elements. A survey of Simple Sequence Repeats (SSRs) identified 584,615 SSRs, with 236,123 sequences containing SSRs. Utilizing the KEGG database, biosynthesis pathways for catechin and epicatechin within the flavonoid synthesis pathway were identified. This comprehensive genomic analysis of Saraca asoca (Sita Ashoka) provides critical insights for conservation efforts aimed at preserving this vulnerable species, Saraca asoca (Roxb.) Willd.

genomics↗

Anti-diabetic and anti-adipogenic effects of polyherbal formulation Varanadi kashayam with a focus on incretin modulation

BackgroundFrontiers of health science increasingly emphasizes systems and network medicine approaches for managing complex lifestyle diseases such as diabetes. In this context, systemic targets like incretin hormones and their modulators - particularly DPP4 inhibitors - have gained prominence. Ayurveda, the Indian System of Medicine (ISM), with its clinically validated multicomponent formulations offers a valuable resource for integrative therapeutic strategies with systemic mode of action. PurposeThe study investigates the incretin modulatory effect of Varanadi Kashayam (VA), an Ayurveda polyherbal formulation used in the clinical management of diabetes and its comorbidities. Experimental approachA high-fat diet induced Sprague-Dawley (SD) rat model was used to study the anti-diabetic, GLP-1 secretory, and anti-obesity effects of VA. In vitro studies using GLUTag cells assessed the GLP-1 secretion and DPP4 gene expression modulation; and studies using 3T3-L1 fibroblasts examined the anti-adipogenic effects. Computational methods including molecular docking and molecular dynamic simulations were used to identify the phytochemicals responsible for DPP4 inhibition. ResultsVA administration significantly improved fasting blood glucose and oral glucose tolerance in experimental animals, along with enhanced GLP-1 secretion. The in vitro results showed inhibition of DPP4 enzyme activity, increase in GLP-1 secretion and downregulation of DPP4 gene expression in GLUTag cells, and suppression of adipogenesis in 3T3-L1 fibroblast cells. Computational analyses ascertained Chebulinic acid, Chebulagic acid and Terchebin as top ranked phytochemicals responsible for DPP4 inhibition effect. ConclusionCombining in vitro, in vivo and in silico findings, this study provides valuable insight into the incretin modulatory effect of VA in treating diabetes and associated metabolic diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/601306v2_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1d424fcorg.highwire.dtl.DTLVardef@c84555org.highwire.dtl.DTLVardef@40094borg.highwire.dtl.DTLVardef@225272_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIVaranadi Kashayam (VA) improved blood glucose and GLP-1 levels in diabetic rats. C_LIO_LIInhibited DPP4 activity and gene expression in GLUTag cells. C_LIO_LISuppressed adipogenesis and adipogenic markers in 3T3-L1 cells. C_LIO_LIChebulinic acid, Chebulagic acid, and Terchebin identified as key DPP4 inhibitors. C_LI

cell biology↗

In vitro and in silico analysis proving DPP4 inhibition and diabetes associated gene network modulation by a polyherbal formulation - Nisakathakadi Kashaya.

Frontiers of disease biology started recognizing the importance of systems and network medicine approach for managing chronic disease like diabetes. Dipeptidyl-peptidase IV (DPP4) inhibitors are one such class of anti-diabetic drugs recognized for their systemic biological actions. Polyherbal preparations like Ayurveda formulations are ideal for identifying novel DPP4 inhibitors having greater efficacy and safety profile. Additionally, expanding the research on the multitargeted mode of action of these polyherbal formulations can render novel insights into the complex biology of disease manifestations. The current study aims at identifying DPP4 inhibitory potential of a clinically established Ayurveda anti-diabetic formulation Nisakathakadi Kashaya (NK) using in vitro and in silico methods as well as the modulation of diabetes associated gene network by NK. a. Standard enzyme inhibition assay was used to study the DPP4 inhibitory potential of NK, followed by bioinformatics and computational biology tools for identifying the potential bioactives and their molecular interactions involved in DPP4 inhibition. STITCH, CHEMBL and BindingDB databases were used for target mapping and depicting the multi-targeted network pharmacology interaction of NK and the formulation. EnrichR was used to depict a sub-network of diabetes proteins and their relationship with diabetes associated comorbidities. NK demonstrated a dose dependent DPP4 inhibition with an IC50 of 2.06 g GAE/mL. Molecular docking identified three compounds namely Terchebin, Locaracemoside B and 1,2,4,6 Tetra o Galloyl Beta D Glucose showing stable interactions with DPP4 similar to the standard drug Vildagliptin. The network pharmacology analysis of NK identified a number of targets like TNF, TGF{beta}1, SOD1, SOD2, AKT1, DPP4 and GLP1R in its protein-protein interaction network which are vital to diabetic progression and complications. The present work demonstrated that the polyherbal formulation NK has DPP4 inhibition potential and modulates a large number of diabetes related proteins and pathways. The approach adopted in the current study by combining in vitro and in silico methods allowed us to understand the mechanism of DPP4 inhibition by the formulation and also the possible pharmacological networking through which the formulation exert its systemic effect in diabetes management.

systems biology↗