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Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with subsequent damage to the bone joints with a global incidence rate of 0.5–1%. To combat with RA various commercially available anti-inflammatory drugs like non-steroidal anti-inflammatory drugs (NSAIDs) are commonly practiced; however, their long-term exposure often results in eliciting gastrointestinal and renal toxicity. Given this, the scientific communities are searching for an alternative therapeutic option that seems less injurious and equally efficacious. Equisetum diffusum D. Don, from the Equisetaceae family, is a native pteridophyte species of the sub-Himalayan region of India and has been reported to have a diverse array of pharmacological properties. The decoction and macerated whole plant extract has been used by various tribal communities (like Tagin, Galo, Adi, Kukis, Meiteis, Mulam) throughout the tropical and sub-tropical Asian countries for the treatment of arthritis, bone fractures, back pain, and abrasives. The present research is focused on determining the anti-arthritic potential of E. diffusum whole plant methanol extract (EDME) in adjuvant-induced arthritic rats. Oral administration with 250 and 500 mg/kg b.w. doses of EDME significantly restored paw-edema, arthritic scoring, and normal body weight. EDME treatment also normalized the haematological, biochemical, radiological, and histological status when compared to the arthritic control rats. The methanol extract significantly ( p  < 0.05) attenuated arthritis progression by downregulating the gene expression of pro-inflammatory mediators, like COX-2, TNF-α, IL-6, and upregulating the expression of anti-inflammatory mediators PPAR-γ, Iκβ in the blood, in a dose-dependent manner. Significantly, EDME also reduced the serum concentration of COX-2, TNF-α, and IL-6 compared to arthritic control rats ( p  < 0.05). The treatment with EDME also normalized the oxidative stress level in liver by restoring the GSH level, CAT and SOD activities and reducing the elevated MDA level. HPTLC and LC–MS/MS analyses of EDME confirmed the presence of potent polyphenols (chlorogenic acid, 4-hydroxycinnamic acid) and flavonoids (kaempferol), thereby suggesting the anti-arthritic property of the plant. All our findings established the anti-arthritic potential of E. diffusum extract in chronic arthritis model on a strong ground.

Rhizomes of Drynaria quercifolia have long been traditionally used to manage rheumatic pain. However, there is limited research supporting this traditional practice and insufficient evidence demonstrating the molecular mechanisms of action of plant-derived bioactives in rheumatoid arthritis (RA). The current study aims to identify the effective components in Drynaria quercifolia methanol rhizome extract (DME) and their probable pharmacological mechanisms in alleviating Rheumatoid Arthritis (RA) using network-pharmacology, molecular docking, molecular-dynamics simulations, and gene expression-based validation. Gas chromatography–mass spectrometry (GC-MS) based screening identified 41 volatile phytocomponents from DME having drug-like potentiality. Network pharmacology-based screening revealed 117 therapeutic targets for RA of which 11 have been identified as core targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that key target genes were mostly enriched in the inflammatory response associated with multiple signalling pathways. Molecular docking and molecular dynamics studies revealed that key target proteins like serine/threonine-protein kinase (AKT1), peroxisome proliferator-activated receptor alpha (PPARA), and peroxisome proliferator-activated receptor gamma (PPARG), exhibited strong binding affinity and stable interactions with multiple phytocomponents present in DME. For experimental verification FCA (Freund’s complete adjuvant)-induced chronic arthritis model employed for further molecular investigation. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) results validated that DME significantly ( p  ≤ 0.05) regulate the expression of key identified target genes AKT and PPARG in experimental RA model. Moreover, this study further confirmed that DME significantly ( p  ≤ 0.05) downregulated pro-inflammatory mediators like COX-2, IL-6 and TNF-α at gene and protein levels and also normalized ( p  ≤ 0.05) different oxidative stress parameters in both the low and high dose groups of DME-treated arthritic animals. In conclusion, the network-based in silico approach indicated that the phytocomponents present in DME probably act in a synergistic way to modulate key identified targets associated with RA, which was further validated by experimental studies. Therefore, DME could be a potential alternative in immunomodulatory therapies to combat RA and related chronic inflammatory conditions.

Background The fronds of Drynaria quercifolia have traditionally been used in rheumatic pain management. The goal of the present study was to validate the potent anti-inflammatory and anti-rheumatoid properties of the methanolic-extract of its rhizome using in vitro, in vivo and in silico strategies. Methods The plant was collected and the methanolic extract was prepared from its rhizome. Protein denaturation test, hypotonicity and heat-induced haemolysis assays were performed in vitro. The in vivo anti-rheumatoid potential was assessed in Freund’s complete adjuvant (FCA)-induced Wistar rat model through inflammatory paw-edema, haematological, biochemical, radiological and histopathological measurements. Moreover, metabolites of methanolic extract were screened by gas chromatography-mass spectrometry (GC-MS) and 3D molecular structures of active components were utilized for in silico docking study using AutoDock. Results In vitro results evinced a significant ( p  < 0.05) anti-inflammatory activity of the rhizome methanolic extract in a dose-linear response. Further, Drynaria quercifolia rhizome methanolic extract (DME) significantly ameliorated rheumatoid arthritis as indicated by the inhibition of arthritic paw-edema (in millimeter) in the rat rheumatoid arthritis models in both the low (57.71 ± 0.99, p  < 0.01) and high dose groups (54.45 ± 1.30, p  < 0.001) when compared to arthritic control. Treatment with DME also normalized the haematological (RBC, WBC, platelet counts and hemoglobin contents) and biochemical parameters (total protein, albumin, creatinine and ceruloplasmin) significantly ( p  < 0.05), which were further supported by histopathological and radiological analyses. Furthermore, GC-MS analysis of DME demonstrated the presence of 47 phytochemical compounds. Compounds like Squalene, Gamma Tocopherol, n-Hexadecanoic acid showed potent inhibition of cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukin (IL-6) in the docking analysis. Conclusion Results from in vivo and in vitro studies indicated that DME possesses a potent anti-inflammatory and anti-arthritic activity. In silico studies delineated the emergent potent inhibitory effects of several bio-active components on the target inflammatory markers (COX-2, TNF-α and IL-6).

Background Aloe vera leaf gel has proven efficacious roles in the amelioration of several human diseases and illness-conditions. Specific purified gel-derived bio-constituents as well as the naturally harvested unprocessed A. vera gel have shown promise in modifying systemic inflammation. However, the synergistic role of natural herbal remedies, a mainstay of traditional Indian Ayurveda, has not been evaluated rigorously in this plant. In this study, the prevention of membrane lysis and protein denaturation in the presence of A. vera gel homogenate up to the concentration of 1000 μg/ml of gel has been assessed in vitro. Also, regulation of expression of inflammation-mediator genes (TNF-α and Cox-2) has been investigated in vivo in Freund’s complete adjuvant (FCA)-induced inflammatory arthritic Wistar albino rats in a 28-day long study following the daily oral supplementation of Aloe vera gel homogenate doses up to 0.40 and 0.80 g/kg body weight (low-dose and high-dose groups respectively). Results Our results indicated that A. vera gel homogenate inhibits hypotonicity-induced (74.89 ± 1.26%) and heat-induced (20.86 ± 0.77%) RBC membrane lyses respectively at a concentration of 1000 μg/ml, compared to indomethacin standard (80.52 ± 0.65% and 43.98 ± 1.52% respectively at 200 μg/ml concentration). The similar concentration of gel also showed 39.35 ± 4.25% inhibition of protein denaturation compared to standard diclofenac sodium (46.74 ± 1.84% at 100 μg/ml concentration) in vitro. When assessed in vivo, TNF-α expression was found to be decreased by 35.88% and 38.52%, and Cox-2 expression was found to be decreased by 31.65% and 34.96%, in low-dose and high-dose groups respectively, when compared to the arthritic controls. Conclusions Our findings justify the role of unprocessed A. vera gel homogenate in preventing tissue damage and in the downregulation of TNF-α and Cox-2 gene expressions for the immune-modulation of inflammatory arthritis condition.

Background Equisetum diffusum D. Don commonly known as ‘Himalayan horsetail’, has been traditionally used in the treatment of back pain, bone fracture and dislocation, and arthritis by various tribal communities of India. Our previous study confirmed the anti-inflammatory efficacy of the plant through in silico, in vitro , and in vivo model studies. Therefore, the current research is focused on safety dose evaluation for the first-time of the whole-plant methanol extract (EDME) of E. diffusum through appropriate in silico, in vitro, and in vivo approaches. Method The whole plant, along with its rhizomes, was collected, and the methanol extract was prepared. The in silico ADMET study was performed to predict the pharmacokinetics profile and toxicity of all the identified phyto-compounds of EDME previously screened by GC–MS study. In vitro cytotoxicity study of EDME was performed using two cell lines: kidney (HEK293) and liver (Huh7) cell lines. The in vivo toxicity study of EDME was validated by the acute toxicity (OECD 423, 2002) and sub-acute toxicity assays (OECD 407, 2008) in the Wistar Albino rat model. Results The in silico ADMET study of all 47 bioactives predicted good pharmacokinetic and low toxicity profiles. In vitro cytotoxicity showed higher IC 50 values of EDME viz., 672 ± 15.7 μg/mL and 1698 ± 6.54 μg/mL for both kidney (HEK293) and liver (Huh7) cell lines, respectively, which were considered as low-toxic. Based on acute oral toxicity, the LD 50 value of the extract was considered “non-toxic” up to a feeding range of 2000 mg/kg of body weight. The regular consumption of the extract for an extended period (28 days) was also qualified as safe based on the body and organ weight, hematological, biochemical, and histoarchitecture results in the sub-acute toxicity assay. Conclusion The detailed in silico , in vitro , in vivo (acute and sub-acute oral toxicity) studies gave us a new insight to the safety dose evaluation of Equisetum diffusum , which may serve as a reliable documentation for undertaking the experimental validation of the ethnobotanical uses of the plant which would help in the field of drug development for the treatment of inflammation related complications.

Background There is always an increasing demand for natural remedies from natural sources which can substitute the synthetic therapeutic drugs and lessen their side effects. The present study aims to investigate the antioxidant, anti-inflammatory, antimicrobial properties and in silico docking study of Citrus macroptera leaf (CML) extract in both in vivo and in vitro aspect. Material and methods The antioxidant and anti-inflammatory potential of crude extract was investigated in vitro and in vivo on Wistar albino rat. The antioxidant potentiality also investigated on HepG2 cell line. Antimicrobial activity was evaluated against Staphylococcus sp. and Klebsiella sp. Chemical compounds of the crude extract were identified by GC-MS analysis. In silico docking was also done against NF-ҡB protein. Results At 200 μg/ml concentration, CML significantly scavenges reactive oxygen species (ROS) which was generated on HepG2 cell line. CML showed 71% anti-inflammatory activity ( p ≤ 0.001) against carrageenan-induced paw edema in albino Wistar rats. CML extract is very effective against staphylococcus sp. than Klebsiella sp. In the docking analysis, the proximadiol and menthone had − 5.6 kcal/mol and − 5.7 kcal/mol binding affinity with the protein NF-ҡB. Conclusion In the present work, CML provided notable antioxidant, anti-inflammatory, and antimicrobial activity. This activity was confirmed by both in vitro and in vivo followed by in silico docking technique. Overall, the experimental results presented in this study suggest that crude extract of CML could be used as a promising antioxidant and anti-inflammatory candidate with potential benefits.

Background: The flower of Acmella uliginosa (AU) (Sw.) Cass., a naturally grown herb in India, is consumed as a natural painkiller for its notable analgesic properties. Objective: The objective of the study was to establish the role of AU flower methanolic extract in antinociception and its neuromodulatory activities to assess any disadvantage of the drug akin to opioids. Materials and Methods: In experimental rats, plant flower extracts were fed at a dose of 100 mg and 200 mg/kg body weight (BW) for 14 days. Analgesic activity was evaluated through formalin-induced paw licking test. T-maze, novel object recognition (NOR), and rotarod tests were done to assess the role of the extract in memory alteration and neuromotor coordination, respectively. Acetylcholinesterase (AChE), reduced glutathione (GSH), and superoxide dismutase (SOD) activity from the brain homogenates were done to assess the induced oxidative stress. Results: The plant proved to be a promising analgesic when fed orally up to 200 mg/kg BW dose. No acute toxicity was seen up to 1000 mg/kg. In the T-maze test, extract-fed animals showed a reduction in food searching time. In NOR test, the discrimination index between new and familiar objects was high in extract-fed animals compared to standard group. In rotarod test, the extract did not alter the neuromotor coordination. AChE, GSH, and SOD activities were normal in extract-treated animals. Conclusion: Memory alteration and oxidative stress are two major drawbacks associated with opioid drugs. Our results indicate that the AU flower methanolic extract qualifies as a potent painkiller and overcomes the disadvantages of opioid analgesics.

Leptin, an adipokine related to obesity, is mainly known for its role in regulating energy homeostasis and appetite by working via the leptin receptor. Recently, different groups have demonstrated that apart from adipocytes, specific cell types associated with cancer and tumor microenvironments express leptin and leptin receptors. This tumor microenvironment-associated leptin-leptin receptor signaling contributes to the different hallmarks of cancer, ranging from inflammatory changes to metastasis. Eventually, it has also been reported that high serum level of leptin, a characteristic of obese people, is linked to enhanced tumor growth. On the other hand, leptin can influence both innate as well as adaptive immunity related to cancer. Overall, leptin's role in modulating cancer is controversial. So, in this review, we summarized the role of leptin in shaping different forms of cancer that are influenced by leptin-leptin receptor signaling with special emphasis on immunomodulation and inflammatory events and also discussed the possible therapeutic interventions to date. As this review work, with the collection of different updated knowledge, has summarized the role of leptin on cancer, it would be useful material to have on hand for both beginners as well as pioneers of these and related fields.Leptin, an adipokine related to obesity, is mainly known for its role in regulating energy homeostasis and appetite by working via the leptin receptor. Recently, different groups have demonstrated that apart from adipocytes, specific cell types associated with cancer and tumor microenvironments express leptin and leptin receptors. This tumor microenvironment-associated leptin-leptin receptor signaling contributes to the different hallmarks of cancer, ranging from inflammatory changes to metastasis. Eventually, it has also been reported that high serum level of leptin, a characteristic of obese people, is linked to enhanced tumor growth. On the other hand, leptin can influence both innate as well as adaptive immunity related to cancer. Overall, leptin's role in modulating cancer is controversial. So, in this review, we summarized the role of leptin in shaping different forms of cancer that are influenced by leptin-leptin receptor signaling with special emphasis on immunomodulation and inflammatory events and also discussed the possible therapeutic interventions to date. As this review work, with the collection of different updated knowledge, has summarized the role of leptin on cancer, it would be useful material to have on hand for both beginners as well as pioneers of these and related fields.

Leptin, an adipokine related to obesity, is mainly known for its role in regulating energy homeostasis and appetite by working via the leptin receptor. Recently, different groups have demonstrated that apart from adipocytes, specific cell types associated with cancer and tumor microenvironments express leptin and leptin receptors. This tumor microenvironment-associated leptin-leptin receptor signaling contributes to the different hallmarks of cancer, ranging from inflammatory changes to metastasis. Eventually, it has also been reported that high serum level of leptin, a characteristic of obese people, is linked to enhanced tumor growth. On the other hand, leptin can influence both innate as well as adaptive immunity related to cancer. Overall, leptin’s role in modulating cancer is controversial. So, in this review, we summarized the role of leptin in shaping different forms of cancer that are influenced by leptin-leptin receptor signaling with special emphasis on immunomodulation and inflammatory events and also discussed the possible therapeutic interventions to date. As this review work, with the collection of different updated knowledge, has summarized the role of leptin on cancer, it would be useful material to have on hand for both beginners as well as pioneers of these and related fields.

A practical and convenient decarbonylation of a variety of aromatic, heteroaromatic, and alkenyl aldehydes by using palladium nanoparticles supported on novel, fibrous nanosilica, named KCC‐1‐PEI/Pd, has been developed. Complete conversion of aldehyde functionalities into deformylated products was achieved in all cases and in nearly all cycles tested by reusing the catalyst systems. This method eliminates further purification of products after their isolation. Syntheses of at least three different deformylated products have been shown in sequence with the same catalyst system, which neither requires use of any additives, such as oxidants and bases, nor CO scavengers. More fiber in a catalyst! A practical and convenient decarbonylation of a variety of aromatic, heteroaromatic, and alkenyl aldehydes with palladium nanoparticles supported on novel, fibrous nanosilica, named KCC‐1‐PEI/Pd, has been developed (see figure). Complete conversion of aldehyde functionalities into deformylated products is achieved and this method eliminates further purification of products after isolation.