Beyond conventional antibiotics approaches: Global perspectives on alternative therapeutics including herbal prevention, and proactive management strategies in bovine mastitis.

Mastitis, an intramammary inflammation resulting from microbial infectious agents, continues to pose a significant challenge within the dairy sector, adversely affecting animal well-being and leading to substantial economic losses. These losses are attributed to decreased milk production, heightened culling rates, and the expenses related to diagnostics, veterinary care, medication, and labor. Moreover, additional costs emerge due to reduced forthcoming milk yields, compromised reproductive health, and increased susceptibility to various illnesses. Identifying the responsible agents is crucial for disease management and the implementation of antimicrobial treatments. Despite the prevalent use of antibiotic treatment, the pressing need for new therapeutic alternatives to combat bovine mastitis arises from limitations, including low cure rates, rising resistance, and the presence of antibiotic residues in milk. This review explores the potential application of herbal extracts and essential oils known for their antimicrobial properties as alternative options for managing pathogens in mastitis treatment. It examines various treatment methods and management strategies, particularly emphasizing the progress of herbal remedies and natural therapeutics in addressing mastitis, a significant concern in bovine populations and dairy herds.

Mechanism of antibacterial phytoconstituents: an updated review.

The increase of multiple drug resistance bacteria significantly diminishes the effectiveness of antibiotic armory and subsequently exaggerates the level of therapeutic failure. Phytoconstituents are exceptional substitutes for resistance-modifying vehicles. The plants appear to be a deep well for the discovery of novel antibacterial compounds. This is owing to the numerous enticing characteristics of plants, they are easily accessible and inexpensive, extracts or chemicals derived from plants typically have significant levels of action against infections, and they rarely cause serious adverse effects. The enormous selection of phytochemicals offers very distinct chemical structures that may provide both novel mechanisms of antimicrobial activity and deliver us with different targets in the interior of the bacterial cell. They can directly affect bacteria or act together with the crucial events of pathogenicity, in this manner decreasing the aptitude of bacteria to create resistance. Abundant phytoconstituents demonstrate various mechanisms of action toward multi drug resistance bacteria. Overall, this comprehensive review will provide insights into the potential of phytoconstituents as alternative treatments for bacterial infections, particularly those caused by multi drug resistance strains. By examining the current state of research in this area, the review will shed light on potential future directions for the development of new antimicrobial therapies.

Bioprospective Role of Ocimum sanctum and Solanum xanthocarpum against Emerging Pathogen: Mycobacterium avium Subspecies paratuberculosis: A Review.

Mycobacterium avium subspecies paratuberculosis (MAP) is a chronic, contagious, and typically life-threatening enteric disease of ruminants caused by a bacterium of the genus Mycobacterium, but it can also affect non-ruminant animals. MAP transmission occurs through the fecal-oral pathway in neonates and young animals. After infection, animals generate IL-4, IL-5, and IL-10, resulting in a Th2 response. Early detection of the disease is necessary to avoid its spread. Many detection methods, viz., staining, culture, and molecular methods, are available, and numerous vaccines and anti-tuberculosis drugs are used to control the disease. However, the prolonged use of anti-tuberculosis drugs leads to the development of resistance. Whereas vaccines hamper the differentiation between infected and vaccinated animals in an endemic herd. This leads to the identification of plant-based bioactive compounds to treat the disease. Bioactive compounds of Ocimum sanctum and Solanum xanthocarpum have been evaluated for their anti-MAP activity. Based on the MIC50 values, Ursolic acid (12 µg/mL) and Solasodine (60 µg/mL) were found to be suitable for anti-MAP activity.

Bioactive components and anti-diabetic properties of Moringa oleifera Lam.

Moringa oleifera Lam. is a perennial tropical deciduous tree with high economic and pharmaceutical value. As an edible plant, M. oleifera Lam. is rich in nutrients, such as proteins, amino acids, mineral elements and vitamins. Besides, it also contains an important number of bioactive phytochemicals, such as polysaccharides, flavonoids, alkaloids, glucosinolates and isothiocyanates. M. oleifera for long has been used as a natural anti-diabetic herb in India and other Asian countries. Thus, the anti-diabetic properties of Moringa plant have evolved highly attention to the researchers. In the last twenty years, a huge number of new chemical structures and their pharmacological activities have been reported in particularly the anti-diabetic properties. The current review highlighted the bioactive phytochemicals from M. Oleifera. Moreover, evidence regarding the therapeutic potential of M. oleifera for diabetes including experimental and clinical data was presented and the underlying mechanisms were revealed in order to provide insights for the development of novel drugs.

Development of Synergy-Based Combination of Methanolic Extract of Andrographis paniculata and Berberis aristata Against E. coli and S. aureus.

This study evaluates the antibacterial activity and phytochemical characterizations of Andrographis paniculata extract (APE) and Berberis aristata extract (BAE). The stem of Andrographis paniculata (AP) and root of Berberis aristata (BA) were extracted with methanol. The results confirmed that APE and BAE possess high phenolic and flavonoid content. The antioxidant activity of the APE and BAE showed an elevated potential to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals with IC50 of 95.03 µg/mL and 256.26 µg/mL, respectively. A total of 35 and 32 metabolites in APE and BAE, respectively, were identified through mass spectrometry analysis, whereas 17 and 12 metabolites in APE and BAE, respectively, were detected through high-performance thin-layer chromatography (HPTLC) fingerprinting profiling. Antibacterial activity of the extracts was performed by the well diffusion and microdilution method, and the findings showed that APE and BAE had antibacterial activities against E. coli and S. aureus. The growth curve and time-kill study showed that the extracts had a bacteriostatic effect. A combination study with the standard drug was carried out using the microdilution checkerboard method in which most of the combinations showed synergistic interactions. The findings of this study have shown that APE and BAE are good sources of antibacterial compounds and can be used for treating infectious diseases caused by E. coli and S. aureus.

Ursolic Acid and Solasodine as Potent Anti-Mycobacterial Agents for Combating Paratuberculosis: An Anti-Inflammatory and In Silico Analysis.

Mycobacterium avium subspecies paratuberculosis (MAP) infection in domestic livestock causes persistent diarrhea, weight loss, and death and is also a potential cause of Crohn's disease (CD) in humans; notably, treatments against MAP are insufficient, costly, and can cause adverse reactions. Hence, plant-derived bioactive constituents have been taken into consideration in this regard. Herein, we present the results of two bioactive constituents (Solasodine and Ursolic acid) that were evaluated for their safety and efficacy against MAP protein (Dephospho-Coenzyme A kinase (DPCK) by utilizing in vitro assays and different tools of in silico biology. The ADME/t-test, the drug-likeness property test, pharmacophore modelling, and PASS prediction have proven that both the constituents have better binding capacities than the available antibiotic drugs used to target protein inhibition pathways. Through our observations, it can be inferred that these two phytochemicals can be adequately used to treat paratuberculosis, thereby combating inflammatory bowel disorders (IBD) of an autoimmune nature.

Effect of Cichorium intybus seeds supplementation on the markers of glycemic control, oxidative stress, inflammation, and lipid profile in type 2 diabetes mellitus: A randomized, double-blind placebo study.

Diabetes mellitus is associated with increased levels of inflammation and oxidative stress in patients. The aim of the present study was to test the hypothesis that aqueous extract of Cichorium intybus seeds (AECIS) would have add-on beneficial effect in type 2 diabetes mellitus (T2DM). In this double-blind randomized clinical study, 150 subjects were enrolled to assess the add-on efficacy and safety of AECIS in T2DM patients. The subjects were randomized (1:1) to the AECIS (n = 51) and placebo (n = 49) groups. The subjects in both groups continued to take prescribed doses of metformin. The standardization of AECIS was carried out by liquid chromatography-mass spectrometry and phytochemical analysis. The mean hemoglobin A1c (HbA1c) level in the AECIS and placebo groups at baseline was 8.6% and 8.5%, respectively. Mean values of HbA1c at the end of 12 weeks of intervention were 7.42% in the AECIS group (a reduction of 1.18% from baseline) and 8.4% in the placebo group (mean reduction of 0.1% from baseline). Besides, significant reduction in inflammation, oxidative stress, and hypertriglyceridemia was seen in the AECIS group (p < .05). The study shows for the first time that AECIS supplementation ameliorates the disease progression and it is beneficial as a potential adjunct dietary supplement for the management of T2DM.

TLC-bioautography identification and GC-MS analysis of antimicrobial and antioxidant active compounds in Musa × paradisiaca L. fruit pulp essential oil.

INTRODUCTION: The absence of microbial growth and resistance to oxidative deterioration in fruits of Musa × paradisiaca L. (bananas) is an indication of the presence of antimicrobial and antioxidant metabolites. OBJECTIVE: In order to investigate the secondary metabolomic spectrum as well as the active antimicrobial and antioxidants present in essential oils (EOs) from fruits of different geographical areas of M. × paradisiaca, gas chromatography-mass spectroscopy (GC-MS) principal component data correlation analysis is complemented with antimicrobial assays and phytochemical and bioautographic antioxidant fingerprints with thin layer chromatography (TLC). METHODOLOGY: An EO was obtained by steam distillation and subjected to GC-MS and TLC for metabolomic profiling from fruit pulp. The antimicrobial potential was tested in both Escherichia coli as a gram negative and Bacillus subtilis as a gram positive microbe. Potential antioxidant metabolites were identified through TLC-bioautography and GC-MS analysis of active zones. RESULTS: A maximum of 0.56% v/w EO was isolated from fruit pulps of M. × paradisiaca. Minimum inhibitory concentrations (MICs) against B. subtillis and E. coli were 0.25 and 0.35 µg/mL, respectively. Thus, 56 metabolites were identified through GC-MS. The major abundant antimicrobial metabolites found in EOs are α-thujene, γ-terpinene, α- and ß-pinene, sabinene, ß-myrcene, limonene, α-capaene, caryophyllene and (Z,E)-α farnesene. Aceteugenol, palmitic acid, stearic acid, palmitin, and stearin were identified as antioxidant metabolites. Principal component analysis of metabolite data reveals correlations and a clear separation based on metabolites obtained from various areas. CONCLUSION: The data generated using metabolic profiling and cluster analysis helped to identify antimicrobial and antioxidant compounds in M. × paradisiaca.

In vitro and ex vivo approach for anti-urolithiatic potential of bioactive fractions of gokhru with simultaneous HPLC analysis of six major metabolites and their exploration in rat plasma.

CONTEXT: Tribulus terrestris L. (Zygophyllaceae) fruits have long been used in traditional systems of medicine for the treatment of various urinary diseases including urolithiasis. OBJECTIVE: To explore the anti-urolithiatic potential of gokhru and to develop an analytical method for quantitative estimation of metabolites for its quality control. MATERIALS AND METHODS: Aqueous extract of gokhru fruit was prepared through maceration followed by decoction to produce a mother extract, which was further used for polarity-based fractionations. In vitro and ex vivo anti-urolithiatic activity of mother extract and fractions at different concentration (100-1000 µg/mL) were carried out using aggregation assay in synthetic urine and in rat plasma, however, nucleation assay for 30 min was done using confocal microscopy. A simultaneous HPLC method has been developed for quantification of diosgenin, catechin, rutin, gallic acid, tannic acid and quercetin in mother extract and in fractions. RESULTS: The extraction resulted in 14.5% of w/w mother extract, however, polarity-based fractionation yielded 2.1, 2.6, 1.5, 1.3 and 6.1% w/w of hexane, toluene, dichloromethane (DCM), n-butanol and water fractions, respectively. In vitro and ex vivo studies showed a significant anti-urolithiatic potential of n-butanol fraction. Further, HPLC analysis revealed significantly (p < 0.01) higher content of quercetin (1.95 ± 0.41% w/w), diosgenin (12.75 ± 0.18% w/w) and tannic acid (9.81 ± 0.47% w/w) in n-butanol fraction as compared to others fractions. DISCUSSION AND CONCLUSION: In vitro and ex vivo studies demonstrated potent anti-urolithiatic activity of n-butanol fraction which can be developed as new phytopharmaceuticals for urolithiasis. HPLC method can be used for quality control and pharmacokinetic studies of gokhru.

Antithrombocytopenic and immunomodulatory potential of metabolically characterized aqueous extract of Carica papaya leaves.

CONTEXT: Carica papaya Linn. (Caricaceae) leaf (CPL) juice has long been traditionally used in ethnomedicine for dengue fever. OBJECTIVE: The study examines the effects of standardized CPL aqueous extract (SCPLE) on platelet count, extramedullary haematopoiesis (EMH), and immunomodulation in cyclophosphamide (CP)-induced animal model of thrombocytopenia. MATERIALS AND METHODS: The extract was analyzed for myricetin, caffeic acid, trans-ferulic acid, and kaempferol using HPTLC for standardization followed by UPLC-qTOF/MS fingerprinting for metabolite signature. The effects of SCPLE (50 and 150 mg/kg p.o.) on proliferative response of platelet count and total leucocyte count (TLC) were observed up to 14 days in Wistar rat. However, delayed-type hypersensitivity (DTH), haemagglutination titre (HT), and in vivo carbon clearance were examined as immunomodulatory parameters in albino mice at 150 mg/kg p.o. against CP. RESULTS: The quantitative HPTLC estimation of SCPLE showed the presence of myricetin, caffeic acid, trans-ferulic acid, and kaempferol up to 280.16 ± 5.99, 370.18 ± 6.27, 1110.86 ± 2.97, and 160.53 ± 2.48 (µg/g), respectively. Twenty-four metabolites were identified using UPLC-qTOF/MS. Oral administration of SCPLE (150 mg/kg) in thrombocytopenic rats exhibited significant (p < 0.01) increase in thrombocytes (1014.83 × 103 cells/mm3), DTH response (0.16 ± 0.004), and phagocytic index (63.15% increase) as compared to CP-induced thrombocytopenia group. Histopathological studies showed minimal fibrosis in spleen histology. DISCUSSION AND CONCLUSIONS: Results suggest CPL can mediate the release of platelets providing the means for the treatment and prevention of dengue.

Antimicrobial and wound healing potential of Marham-e-Aatshak (A Herb-o-Mineral formulation).

Marham-e-Aatshak (MA) is a Unani ointment, with wide use for treating chronic and infectious wounds since long time. This study was designed to screen the antimicrobial and wound healing potential of MA to validate the ethno-therapeutic claims. The agar diffusion method was used to study the antimicrobial action of MA as well as for all of its ingredients. Inhibition zone diameters were measured and MIC values were calculated. Wound healing activity was studied in models of both, excision and incision wounds. Wound contractibility was measured at different intervals in excision wound model; similarly tensile strength was measured in incision wound model. MA and its ingredients showed remarkable inhibitory activity against most of the organisms. In excision wound, a significantly enhanced wound contraction and significantly reduced epithelialization period was observed. In incision wound, significant increase in the mean breaking strength in the test group was observed. The results indicate that MA is capable of fighting against wound infections and able to potentiate the natural healing process.

A novel monolithic controlled delivery system of resveratrol for enhanced hepatoprotection: nanoformulation development, pharmacokinetics and pharmacodynamics.

The current investigation aims to present a novel solid lipid-based nanoparticulate system of resveratrol (RV) for the effective treatment of liver cirrhosis. A simplified solvent injection method was employed and the Box-Behnken experimental design was applied for optimization to get a window particle size of 150-200 nm having maximum entrapment efficiency as well as % release. Optimized resveratrol solid lipid nanoparticles (RV-SLNs) (SR-1) of appropriate characteristics (particle size = 191.1 ± 10.44 nm; zeta potential= -13.56 ± 4.14 mV; entrapment efficiency = 75.23 ± 3.85%; maximum % release = 80.53 ± 3.99%) were produced. Differential scanning calorimetry and X-ray diffraction studies were carried out which collectively proved the reduced crystallinity and stability enhancing the effect of the SLNs. Improved drug stability was further established by the appreciable shelf-life of the formulation from International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)-recommended accelerated stability studies. In vivo studies revealed nearly five-fold increase in the bioavailability of SR-1 (AUC0→∞=3411 ± 170.34 µg/ml/h) as compared to RV suspension (AUC0→∞=653.5 ± 30.10 µg/ml/h). Pharmacodynamic data exhibited a significant decrease in the serum biomarker enzymes (serum glutamic oxalo-acetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase) after oral administration of RV-SLNs as compared to control and marketed (SILYBON(®)) formulations against paracetamol-induced liver cirrhosis. The effect of the treatment was confirmed by the histopathology of the liver microtome sections. Finally, reverse transcriptase-polymerase chain reaction studies were conducted on isolated liver mRNA from SR-1 treated animals and significant down-regulation of tissue inhibitor of metalloproteinases-1 and nuclear factor-kB was witnessed.

Quantification of phenolic acids and antioxidant potential of inbred, hybrid and composite cultivars of maize under different nitrogen regimes.

Maize (Zea mays L.) is a multipurpose crop, which is immensely used worldwide for its nutritional as well as medicinal properties. This study evaluates the effect of varying concentrations of nitrogen (N) on accumulation of phenolic acids and antioxidant activity in different maize cultivars, including inbreds, hybrids and a composite, which were grown in natural light under controlled temperature (30°C/20°C D/N) and humidity (80%), with sufficient (4.5mM) and low (0.05mM) nitrogen supply. Seeds of different cultivars were powdered and extracted in a methanol:water (80:20) mixture through reflux at 60-75°C, and the extracts obtained were subjected to high performance thin layer chromatography (HPTLC), using ethyl acetate: acetic acid: formic acid: water (109:16:12:31) solvent system for the separation of phenolic acids. Antioxidant activity of the extracts was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and H2O2-scavenging activity assays. At sufficient nitrogen condition, the contents of different phenolic acids were higher in the composite cultivar (8.7 mg g-1 d.wt. in gallic acid to 39.3 mg g-1 d.wt. in cinnamic and salicylic acids) than in inbreds and hybrids. Under low nitrogen condition, the phenolic acids contents declined significantly in inbreds and hybrids, but remained almost unaffected in the composite. The antioxidant activity was also the maximum in the composite, and declined similarly as phenolic acids under low nitrogen supply, showing a significant reduction in inbreds and hybrids only. Therefore, the maize composite has a potential for being used as a nutraceutical in human-health sector.

Gastroprotective mechanism of Paederia foetida Linn. (Rubiaceae)--a popular edible plant used by the tribal community of North-East India.

BACKGROUND: The objective of the present study is to evaluate the gastroprotective activity of Paederia foetida L. leaf for gastric ulcer. METHODS: The methanol extract of P. foetida L. leaves at two different dose levels was investigated for gastroprotective potential by using Indomethacin-pylorus ligation, alcohol induced and water immersion stress induced model in rats. In vitro DPPH* radical scavenging activity and western blot analysis of stomach tissue from pylorus ligatures rats were also carried out. HPTLC analysis was done to understand the phyto-pharmacological relationship. RESULTS: Methanol extract at a dose level of 100 mg/kg and 200 mg/kg body weight showed 72 and 78% ulcer protection when compared to negative control whereas reference drug shown 82% protection in Indomethacin-pylorus ligation model. Further, methanol extract also showed protective effect against 70% v/v ethanol and stress induced gastric ulcer model. About 84% protection as compared to cimetidine (85%) was seen in western blot analysis of stomach tissue from pylorus ligatures rats. HPTLC analysis of methanol extract of P. foetida L. confirmed the presence of ß-sitosterol. In DPPH* radical scavenging activity, the IC50 value was observed to be 43.52 µg/ml. CONCLUSIONS: These observations established the traditional claim and thus Paederia foetida could be a potent gastroprotective agent for use in future. The gastroprotective activity might be mediated by the Nrf2 mediated antioxidant and anti secretory effects.

Terminalia arjuna (Roxb.) Wight & Arn. augments cardioprotection via antioxidant and antiapoptotic cascade in isoproterenol induced cardiotoxicity in rats.

Worldwide, Ischemic heart disease (IHD) affects a large population. Implication of myocardial infarction (MI) and its multiple pathophysiology in cardiac function is well known. Further, isoproterenol (ISP) is known to induce MI. Today, there is an urgent need for effective drug that could limit the myocardial injury. Therapeutic intervention with antioxidants has been shown useful in preventing the deleterious changes produced by ISP. Here, we investigated the protective effects of oral pre-treatment of hydroalcoholic extract of bark of Terminalia arjuna (HETA) on biochemical and apoptotic changes during cardiotoxicity induced by isoproterenol (ISP) in rats. HETA was orally administered at a dose of 100, 200 and 400 mg/kg body wt., for 30 days with concurrent administration of ISP (85 mg/kg body wt.) on days 28th and 29th at an interval of 24 h. ISP caused deleterious changes in the myocardium and significantly increased (P < 0.05) malondialdehyde, serum glutamate oxaloacitate transaminase, creatine kinase-MB, lactate dehydrogenase and troponin-I. However, it significantly decreased (P < 0.05) glutathione and superoxide dismutase compared to healthy control. Oral pre-treatment of HETA for 30 days significantly decreased (P < 0.05) the biochemical parameters of oxidative stress and cardiac markers as compared to ISP control. Histopathological findings also revealed that architecture of the myocardium was restored towards normal in HETA pre-treated group. Overall, the present study has shown that the hydroalcoholic extract of bark of T. arjuna (HETA) attenuates oxidative stress, apoptosis and improves antioxidant status in ISP-induced cardiotoxicity in rats.

Solid lipid nanoparticles of anticancer drug andrographolide: formulation, in vitro and in vivo studies.

Diterpenoidal anti-cancer drug andrographolide (AD) was encapsulated into solid lipid nanoparticle (SLN) because of poor aqueous solubility and high lipophilicity. AD-SLNs were prepared by solvent injection method and characterized for droplet size, surface morphology, zeta potential, etc. In vitro drug release was carried out by dialysis-membrane method. A pharmacokinetic study was performed by UPLC/Q-TOF-MS method to determine the maximum plasma concentration (Cmax), area under the curve (AUC), etc. There was an improvement in Cmax and AUC of AD-SLNs when compared with AD, thereby enhancing the bioavailability of AD. The tmax was increased than that of AD suspension, indicating the sustained release pattern of AD-SLNs. The antitumor activity was carried out on Balb/c mice showing better results with AD-SLNs as compared to AD. Thus, the AD-loaded SLNs would be useful for delivering poorly water-soluble AD with enhanced bioavailability and improved antitumor activity.

Hallmarks of diabetes mellitus and insights into the therapeutic potential of synergy-based combinations of phytochemicals in reducing oxidative stress-induced diabetic complications.

Diabetes mellitus (DM) is a serious health issue and is still one of the major causes of mortality around the globe. Natural products have progressively integrated into modern, advanced medical practices. Phytoconstituents from some medicinal plants have demonstrated therapeutic activity in treating different metabolic disorders and have been used to treat DM and its severe complications. The present review provides details of the major anti-diabetic targets identified in the literature and also provides comprehensive information regarding the therapeutic role of a synergy-based combination of phytoconstituents that functions by controlling specific molecular pathways synchronously by inhibiting certain key regulators involved in the development and progression of DM. The review also implicated the role of oxidative stress in diabetic complications and presented scientific validations of phytochemicals and their synergy-based combination using in vitro and or in vivo approaches.

Unravelling the role of dipeptidyl peptidases-8/9 (DPP-8/9) in inflammatory osteoporosis: a comprehensive study investigating chrysin as a potential anti-osteoporotic agent.

OBJECTIVES: This study aimed to investigate the role of dipeptidyl peptidase-8 and 9 (DPP-8/9) enzymes in inflammatory bone loss using a 4-vinylcyclohexene diepoxide (VCD)-induced model in Wistar rats. Additionally, we evaluated the therapeutic potential of inhibiting these enzymes with the flavonoid chrysin. METHODS: Inflammatory osteoporosis was induced by administering VCD that elevated interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) levels. DPP-8/9 enzyme expression and various bone markers were assayed using serum. Further analysis included bone microarchitecture, histology, and immunohistochemistry. Additionally, chrysin's potential to inhibit DPP-8/9 and mitigate VCD-induced inflammatory bone loss was also evaluated. KEY FINDINGS: VCD administration in rats caused ovotoxicity that increased IL-6 and TNF-α levels, resulting in significant bone loss. Serum analysis revealed elevated bone resorption markers and DPP-8/9 enzyme levels. Inhibiting DPP-8/9 with 1G244 reversed these effects, confirmed by histology, immunohistochemistry, and micro-CT scans. Moreover, chrysin significantly reduced DPP-8/9 levels compared with the untreated group, improved bone markers, and lower inflammatory cytokines, indicating reduced osteoclastogenesis. CONCLUSION: This study highlights the role of DPP-8/9 in inflammation-induced osteoporosis. Following inhibition of DPP-8/9, we observed improved bone markers with preservation of trabecular bone mineral density in rats. Additionally, chrysin demonstrated potential as an anti-DPP-8/9 agent, suggesting its viability for future therapeutic interventions in DPP-8/9-related inflammatory diseases.

A comprehensive review on Phyto-MAP: A novel approach of drug discovery against Mycobacterium avium subspecies paratuberculosis using AYUSH heritage.

ETHNOPHARMACOLOGICAL RELEVANCE: Indian system of Traditional medicine, AYUSH (Ayurveda, Yoga, Unani, Siddha, and Homeopathy) has great potential with a History of Safe Use (HOSU) of thousands of medicinal plants included in pharmacopoeias. The multi-targeted approach of phytoconstituents present in different traditionally used medicinal plants makes them suitable candidates for research against various infective pathogens. MAP which is a dairy-borne pathogen is associated with the development of Johne's disease in ruminants and Crohn's disease like autoimmune disorders in human beings. There are no reliable treatment alternatives available against MAP, leaving surgical removal of intestines as the sole option. Hence, there exists an urgent need to search for leads against such infection. AIM OF THE STUDY: The present review has been conducted to find out the ethnopharmacological evidence about the potential of phytoconstituents against Mycobacterium avium subspecies paratuberculosis (MAP), along with the proposal of a potential phyto-MAP mechanism for the very first time taking anti-inflammatory, immunomodulatory, and anti-microbial traditional claims into consideration. MATERIALS AND METHODS: We have analyzed and reviewed different volumes of the two main traditional scriptures of India i.e. Ayurvedic Pharmacopoeia of India (API) and Unani Pharmacopoeia of India (UPI), respectively-for identification of potential anti-MAP plants based on their claims for related disorders. These plants were further investigated systematically for their scientific publications of the last 20 years (2002-2022) available through electronic databases including Google Scholar, Pubmed, and Scopus. The studies conducted in vitro, cell lines, and in vivo levels were taken into consideration along with the associated mechanisms of phytoconstituents. RESULTS: A total of 70 potential medicinal plants have been identified. Based on the ethnopharmacology, a potential phyto-paratuberculosis (Phyto-paraTB) mechanism has been proposed and out of 70, seven potential anti-MAP plants have been identified to have a great future as anti-MAP. CONCLUSION: A novel and scientifically viable plan has been proposed for addressing anti-MAP plants for stimulating research against MAP and related disorders using mass-trusted AYUSH medicine, which can be used as an alternative remedy in resistance cases otherwise can be advocated as an adjuvant with modern treatments for better management of the disease.

Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis.

OBJECTIVES: Piperine, a main component of Piper species, is a plant alkaloid with a long history of medical use in a variety of inflammatory disorders like rheumatoid arthritis. Due to side effects in current treatment modalities of rheumatoid arthritis, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. The aim of this work was to evaluate the anti-inflammatory and antiarthritic effects of piperine. METHODS: Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. Piperine was administered at a dose of 100mgkg(-1) and indomethacin at 1mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO), inflammatory mediators (IL-1ß, TNF-α, IL-10 and PGE2) and histological studies in joints. RESULTS: Piperine was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO) studied. Oral administration of piperine resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1ß, TNF-α and PGE2) and increased level of IL-10. The protective effects of piperine against RA were also evident from the decrease in arthritis scoring and bone histology. CONCLUSIONS: In conclusion, the fact that piperine alter a number of factors known to be involved in RA pathogenesis indicates that piperine can be used similar to indomethacin as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.