Promising Anti-inflammatory Activity Research Articles

Engineered Robust Hydrophobic/Hydrophilic Nanofibrous Scaffolds with Drug-Eluting, Antioxidant, and Antimicrobial Capacity.

Multifunctional nanofibrous architectures have attracted extensive attention for biomedical applications due to their adjustable and versatile properties. Electrospun fabrics stand out as key building blocks for these structures, yet improving their mechanobiological and physicochemical performance is a challenge. Here, we introduce biodegradable engineered hydrophobic/hydrophilic scaffolds consisting of electrospun polylactide nanofibers coated with drug-eluting synthetic (poly(vinyl alcohol)) and natural (starch) polymers. The microstructure of these composite scaffolds was tailored for an increased hydrophilicity, optimized permeability, water retention capacity of up to 5.1 g/g, and enhanced mechanical properties under both dry and wet conditions. Regarding the latter, normalized tensile strengths of up to 32.4 MPa were achieved thanks to the improved fiber interactions and fiber-coating stress transfer. Curcumin was employed as a model drug, and its sustained release in a pure aqueous medium was investigated for 35 days. An in-depth study of the release kinetics revealed the outstanding water solubility and bioavailability of curcumin, owing to its complexation with the hydrophilic polymers and further delineated the role of the hydrophobic nanofibrous network in regulating its release rate. The modified curcumin endowed the composites with antioxidant activities up to 5.7 times higher than that of free curcumin as well as promising anti-inflammatory and bacteriostatic activities. The cytocompatibility and cell proliferation capability on human dermal fibroblasts also evidenced the safe use of the constructs. Finally, the fabrics present pH-responsive color-changing behavior easily distinguishable within the pH range of 5-9. Thus, these designs offer a facile and cost-effective roadmap for the fabrication of smart multifunctional biomaterials, especially for chronic wound healing.

Silibinin as a major component of milk thistle seed provides promising influences against diabetes and its complications: a systematic review.

Silibinin, or silybin, is a polyphenolic flavonoid and the main active component of silymarin, isolated from the seeds of the milk thistle plant (Silybum marianum). It has been shown to have antioxidant, antineoplastic, hepatoprotective, neuroprotective, anti-inflammatory, antimicrobial, and antidiabetic effects. In this systematic review, a literature search was conducted from inception until January 2024 on major electronic databases (PubMed, Scopus, Web of Science, and Google Scholar) to identify studies assessing the effects of silibinin on diabetes and its associated complications in different molecular, cellular, animal, and clinical studies. Silibinin has been shown to improve diabetic conditions through a variety of mechanisms, including reducing insulin resistance (IR), lowering reactive oxygen species (ROS) levels, and affecting glycolysis, gluconeogenesis, and glycogenolysis. Silibinin treatment reduced blood glucose (BG) levels, oxidative stress markers, and inflammatory cytokines while increasing glycosylated hemoglobin (HbA1C) and antioxidative marker levels in various cellular and animal models of diabetes. It also ameliorated levels of triglyceride (TG), cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Furthermore, silibinin has been identified as an effective treatment for diabetic complications, including hepatic damage, endothelial dysfunction, neuropathy, nephropathy, retinopathy, and osteoporosis. The promising anti-inflammatory, antioxidant, antidiabetic, and insulin-sensitizing activities of silibinin were also supported in clinical studies. The administration of silibinin could possess multiple protective impacts in improving DM and its complications. Nevertheless, further well-designed investigations are necessary to better understand its mechanisms.

Six new diterpenoids with anti-inflammatory and cytotoxic activity from Isodon serra

Diterpenoids occupy an important slot of the natural products diversity space with wide ranges of bioactivities and complex structures, providing potential applications for the development of therapeutics. In this study, we reported four new abietane-type diterpenoids viroxocin B-E (1–4), a new totarane-type diterpenoid viroxocin F (5), and a new sempervirane-type diterpenoid viroxocin G (6) along with four known compounds (7–10), isolated and identified from a widely used Traditional Chinese Medicine, Isodon serra (I. serra). Their structures were established by spectroscopic data analysis, experimental and calculated electronic circular dichroism (ECD) data, as well as X-ray diffraction analysis. Compounds 2, 5, 7, 8 and 10 exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 60% at 10 μM. Compound 7 showed cytotoxicity against human renal cell carcinoma 769P at 20 μM, the inhibition rate was 52.66%.

Merging total synthesis and NMR technology for deciphering the realistic structure of natural 2,6-dideoxyglycosides.

The structural identification and efficient synthesis of bioactive 2,6-dideoxyglycosides are daunting challenges. Here, we report the total synthesis and structural revision of a series of 2,6-dideoxyglycosides from folk medicinal plants Ecdysanthera rosea and Chonemorpha megacalyx, which feature pregnane steroidal aglycones bearing an 18,20-lactone and glycans consisting of 2,6-dideoxy-3-O-methyl-β-pyranose residues, including ecdysosides A, B, and F and ecdysantheroside A. All the eight possible 2,6-dideoxy-3-O-methyl-β-pyranoside stereoisomers (of the proposed ecdysantheroside A) have been synthesized that testify the effective gold(I)-catalyzed glycosylation methods for the synthesis of various 2-deoxy-β-pyranosidic linkages and lays a foundation via nuclear magnetic resonance data mapping to identify these sugar units which occur promiscuously in the present and other natural glycosides. Moreover, some synthetic natural compounds and their isomers have shown promising anticancer, immunosuppressive, anti-inflammatory, and anti-Zika virus activities.

18-β-glycyrrhetinic acid-loaded polymeric nanoparticles attenuate cigarette smoke-induced markers of impaired antiviral response in vitro

Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-β-glycyrrhetinic acid (18-β-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-β-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1β), mimicking what happens in smokers and COPD patients. Treatment with 18-β-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1β levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-β-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity.

Does Resveratrol Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is influenced by a variety of factors, including environmental and genetic factors. The most significant outcome is the alteration of free fatty acid and triglyceride metabolism. Lipotoxicity, impaired autophagy, chronic inflammation, and oxidative stress, as well as coexisting insulin resistance, obesity, and changes in the composition of gut microbiota, are also considered crucial factors in the pathogenesis of MASLD. Resveratrol is a polyphenolic compound that belongs to the stilbene subgroup. This review summarises the available information on the therapeutic effects of resveratrol against MASLD. Resveratrol has demonstrated promising antisteatotic, antioxidant, and anti-inflammatory activities in liver cells in in vitro and animal studies. Resveratrol has been associated with inhibiting the NF-κB pathway, activating the SIRT-1 and AMPK pathways, normalizing the intestinal microbiome, and alleviating intestinal inflammation. However, clinical studies have yielded inconclusive results regarding the efficacy of resveratrol in alleviating hepatic steatosis or reducing any of the parameters found in MASLD in human patients. The lack of homogeneity between studies, low bioavailability of resveratrol, and population variability when compared to animal models could be the reasons for this.

Hyaluronic acid from bluefin tuna by-product: Structural analysis and pharmacological activities

The fishing and aquaculture industries generate a huge amount of waste during processing and preservation operations, especially those of tuna. Recovering these by-products is a major economic and environmental challenge for manufacturers seeking to produce new active biomolecules of interest. A new hyaluronic acid was extracted from bluefin tuna's vitreous humour to assess its antioxidant and pharmacological activities. The characterization by infrared spectroscopy (FT-IR), nuclear magnetic resonance ((1D1H) and 2D (1H COSY, 1H/13C HSQC)) and size exclusion chromatography (SEC/MALS/DRI/VD) revealed that the extracted polysaccharide was a hyaluronic acid with high uronic acid content (55.8 %) and a weight average molecular weight of 888 kDa. This polymer possesses significant anti-radical activity and ferrous chelating capacity. In addition, pharmacological evaluation of its anti-inflammatory and analgesic potential, using preclinical models, in comparison with reference drugs (Dexamethasone, diclofenac, and acetylsalicylate of lysine), revealed promising anti-inflammatory activity as well as interesting peripheral and central antinociceptive activity. Therefore, our new hyaluronic acid compound may therefore serve as a potential drug candidate for the treatment of pain sensation and inflammation of various pathological origins.

In vitro Screening of 5-LOX /COX-2 Dual Inhibitors from selected Medicinal plant Maytenus arbutifolia

Background: The clinical management of the inflammatory diseases by using NSAIDs and selective COX-2 inhibitors, shunting arachidonic acid pathway to the 5‐LOX pathway, which is associated with the production of high amount of Leukotrienes and cysteinyl-leukotrienes, which are involved in pathophysiological of various type of cancers and inflammatory diseases. The substantial efforts are being made to the development of dual inhibitors against Cyclooxygenase (COX-2) and 5- Lipoxygenase (5-LOX) should be more growing demand for efficient as anti-inflammatory medicine with lower side effects than the currently available drugs. Maytenus arbutifolia (M. arbutifolia) is medicinal plant belongs to the family Celastraceae, and the leaves of M.arbutifolia have been used for the treatment of skin infections and inflammatory related disease. Objective: The current study aimed to examine the in vitro screening of M. arbutifolia leaf organic extracts for the development of anti-inflammatory agents through evaluate the inhibitory effect on Cyclooxygenase- 1and2 and 5- Lipoxygenases enzymes. Methods: The powdered dried leaves of the M. arbutifolia (100 g) was extracted with successive Soxhlet extraction by using solvents of low polarity (Petroleum ether) to a high polar solvent (Ethanol). These leaf extracts were evaluated for the in vitro anti-inflammatory activity by 5- Lipooxygenase, Cyclooxygenase-1 and Cyclooxygenase-2 inhibitory activities by ELISA method. Results: Among the tested extracts, the ethanolic leaf extracts of M.arbutifolia showed (MALET) potential 5-LOX inhibition i.e.77.58 % at 100µg/ml with IC50 of 23.76µg/ml, and also exhibited two fold COX-2 versus COX-1 inhibition, with potent COX-2 inhibitory effect with IC50 of 30.35μg/ml. The promising anti-inflammatory activity exhibited by MALET was due to the presence of secondary metabolites such as flavonoids, tannins and polyphenolic compounds. Conclusion: The current study concluded that ethanolic leaf extracts of M.arbutifolia is a promising source for isolation of 5-LOX and COX-2 dual inhibitory compound and highlights the potential traditional remedies for managing of inflammatory related diseases and cancers.

Design, synthesis, pharmacological evaluation, and in silico studies of the activity of novel spiro pyrrolo[3,4-d]pyrimidine derivatives.

In the present study, spiro compounds are shown to have distinctive characteristics because of their interesting conformations and their structural impacts on biological systems. A new family of functionalized spiro pyrrolo[3,4-d]pyrimidines is prepared via the one-pot condensation reaction of amino cyclohexane derivatives with benzaldehyde to prepare fused azaspiroundecanedione and azaspirodecenone/thione derivatives. A series of synthesized spiro compounds were scanned against DPPH and evaluated for their ability to inhibit COX-1 and COX-2. All compounds exhibit significant antiinflammatory activity, and they inhibited both COX-1 and COX-2 enzymes with a selectivity index higher than celecoxib as a reference drug. The most powerful and selective COX-2 inhibitor compounds were 11 and 6, with selectivity indices of 175 and 129.21 in comparison to 31.52 of the standard celecoxib. However, candidate 14 showed a very promising antiinflammatory activity with an IC50 of 6.00, while celecoxib had an IC50 of 14.50. Our findings are promising in the area of medicinal chemistry for further optimization of the newly designed and synthesized compounds regarding the discussed structure-activity relationship study (SAR), in order to obtain a superior antioxidant lead compound in the near future. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopic and elemental investigations.

Discovery of dibenzylbutane lignan LCA derivatives as potent anti-inflammatory agents.

Inflammation is the body's response to defence against infection or injury, and is associated with the progression of many diseases, such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). LCA, a dibenzylbutane lignan extracted from the roots of traditional medicinal plant Litsea cubeba (Lour.) Pers., has demonstrated promising anti-inflammatory activity. In this study, a series of novel LCA derivatives were designed, synthesized, and evaluated for anti-inflammatory activity. Lipopolysaccharide (LPS)-induced RAW 264.7 cell model experiments showed that compound 10h (at 20 μM of concentration) had the strongest inhibitory effect on NO release, and inhibited the secretion and gene expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in vitro. In addition, western blot, immunofluorescence, and molecular docking showed that the anti-inflammatory mechanism of compound 10h may be related to the nuclear factor (NF)-κB signalling pathway. In vivo studies based on a carrageenan-induced mouse paw edema model have shown significant anti-inflammatory activity of compound 10h at 20 mg kg-1. Preliminary in vitro and in vivo studies indicate that compound 10h has the potential to be developed as a novel anti-inflammatory agent.

In vitro protective and anti-inflammatory effects of Capparis spinosa and its flavonoids profile

Abstract Multiple beneficial effects have been reported to numerous species of Capparis genus. Among these, Capparis spinosa has exhibited several biological benefits, including anti-inflammatory hepatoprotective, antioxidant, and antidiabetic effects. Herein, C. spinosa was extracted with different solvents and the ability of these fractions to suppress nitric oxide (NO) production in RAW 264.7 cells were assessed via Griess reagent. The effects of C. spinosa fractions on different inflammatory markers were also determined in THP-1 and Human umbilical vein endothelial cells (HUVEC) using reverse transcription polymerase chain reaction. Additionally, high-performance liquid chromatography (HPLC) ultra-violet was employed to estimate the presence of three flavonoid compounds, namely, apigenin, kaempferol, and rutin. Our results indicate that chloroform (CHCl3) and ethyl acetate (EtOAc) fractions of C. spinosa exhibited a promising anti-inflammatory activity via in vitro inhibition of NO in lipopolysaccharide stimulated RAW 264.7 cells. Pretreated stimulated THP-1 cells with either CHCl3 or EtOAc fractions showed decreased expression of interleukin 1 beta (IL-1β) and tumor necrosis factor Alpha in a dose-dependent manner. In HUVEC cells, both fractions downregulate the expression of IL-1β, upregulate the peroxisome proliferator-activated receptor alpha PPAR-α while no significant impact was observed on PPAR-ϒ gene expression. The presence of apigenin, kaempferol, and rutin in the crude extract has been confirmed through HPLC method. Collectively, these results support the ethnopharmacological usage of C. spinosa as a potential therapy for inflammation related conditions including atherosclerosis.

Novel quinazolinone Derivatives: Design, synthesis and in vivo evaluation as potential agents targeting Alzheimer disease

Since Alzheimer disease is one of the most prevalent types of dementia with a high mortality and disability rate, so development of multi-target drugs becomes the major strategy for battling AD. This study shows the development of a series of quinazolinone based derivatives as novel, multifunctional anti-AD drugs that exhibit both cholinesterase inhibitoryand anti-inflammatory properties. The preliminary results of the in vitro AChE inhibition activity showed that compounds 4b, 5a, 6f, 6h and 7b were better represented for further evaluation. Furthermore, in-vivo AChE inhibition activity and behavior Morris water maze test against donepezil as reference drug were evaluated. Additionally, hippocampal inflammatory markers; TNF-α, NFĸB, IL-1β and IL-6 and antioxidant markers; SOD and MDA were assessed to evaluate the efficacy of quinazolinone derivatives against AD hallmarks. The results showed that 6f, 6h and 7b have promising anti-acetylcholinesterase, anti-inflammatory and antioxidant activities thus, have a significant effect in treatment of AD. Moreover, Histopathological examination revealed that 6f, 6h and 7b derivatives have neuroprotective effect against neuronal damage caused by induced scopolamine model in mice. Finally, the binding ability of the synthesized derivatives to the target, AChE was investigated through molecular docking which reflected significant interactions to the target based on their docking binding scores. Hence, the newly designed quinazolinone derivatives possess promising anti-acetylcholinesterase activity and challenging for the management of AD in the future.

Anti-inflammatory activity of verbascoside- and isoverbascoside-rich Lamiales medicinal plants

Verbascoside and isoverbascoside are two active phenylethanoid glycosides mainly found in plants of the order Lamiales. This study analyzes the verbascoside and isoverbascoside levels and the total phenolic contents in the water and ethanolic extracts of 20 medicinal plants of the order Lamiales commonly used in Thailand. The related bioactivities, including the antioxidant activity via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reduction activity potential assays and anti-tyrosinase and -inflammatory activities via the cyclooxygenase and nitric oxide assays are also investigated. The extracts of several plant species, including Barleria prionitis, B. lupulina, Rhinacanthus nasutus, Orthosiphon aristatus, and Nicoteba betonica, exhibit high verbascoside and isoverbascoside content levels. The correlation analysis between the bioactive activities and the active compounds demonstrates a significant association between the verbascoside level in the water extracts and both the DPPH antioxidant activity and the nitric oxide level in the anti-inflammatory assays. This study provides the first report on the verbascoside and isoverbascoside quantification of several plant samples. The findings provide valuable insights for future research on lesser-studied plants possessing high verbascoside and isoverbascoside levels, which exhibit promising anti-inflammatory activities.

Treatment of rheumatoid arthritis with dissymmetric fluorine and pyridyl-substituted 3,5-bis(aryl)-4-piperidone derivatives by inhibition of NF-κB and MAPK activation

Inhibition of inflammation-related NF-κB and MAPK activation could treat rheumatoid arthritis (RA). Previously, some fluorine-substituted 3,5-bis(aryl)-4-piperidone derivatives (BAPs) exhibited promising anti-inflammatory activity. Herein, interesting structural optimization was carried out and generated thirty-eight dissymmetric fluorine and pyridyl-substituted BAPs (4a-s and 5a-s). They were confirmed by NMR and HRMS. A preliminary structure–activity relationship was summarized and discovered 3,5-CF3 and 3-pyridyl-substituted 4k exhibited less toxicity and higher anti-inflammatory activity. Preliminary mechanistic studies revealed that 4k inhibited Lipopolysaccharide-induced nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) activation by suppressing LPS-induced phosphorylation levels of NF-κB/p65, NF-κB/IκBα, c-Jun N-terminal kinase (JNK), extracellular regulated protein kinases (ERK), and NF-κB/p38 in RAW264.7 cells. In vivo, 4k inhibited the development of inflammation and synovial proliferation in rat joint tissues, significantly decreasing paw swelling and arthritis index in adjuvant-induced arthritis rats. More importantly, 4k did not affect body weight and splenic index values. Overall, 4k showed optimistic anti-RA effects, which may be developed as a potential multifunctional agent for the clinical treatment of RA.

ANTI-INFLAMMATORY ACTIVITY OF SIDDHA POLYHERBAL FORMULATION SEVVIYADHI CHOORANAM ON CARRAGEENAN INDUCED PAW EDEMA IN WISTAR ALBINO RATS

Objective: The aim of the study was to explore the anti-inflammatory activity of Siddha polyherbal formulation Sevviyadhi chooranam in Carrageenan induced paw edema in wistar albino rats, and compared with the standard drug Indomethacin. Methods: The Siddha polyherbal formulation Sevviyadhi chooranam indicated for sinusitis was prepared based on GMP (Good Clinical Practice) guidelines. Study procedure was approved by Institutional Animal Ethics Committee (IAEC). The experimental animals were measured for paw edema volume at 1, 2, 3, 4, 5 h using Plethysmometer (Model 7150 UGO Basile, Italy). Edema was expressed as mean increase in paw volume relative to control animals. And then, findings were compared with Indomethacin (Standard drug). Results: The findings revealed that test drug Sevviyadhi chooranam at higher dosage 200 mg/kg (Group V) had equal effect on anti-inflammatory activity with percentage protection of 93.2% when compared with the standard drug Indomethacin at about 40 mg/kg (Group III) with percentage protection 93.2%. However, the test drug Sevviyadhi chooranam at a higher dosage 200 mg/kg (Group V) with a percentage protection 93.2% was highly effective when compared with lower dosage about 100 mg/kg (Group IV) with a percentage protection 27.12%. Hence, the study resulted that the Siddha polyherbal formulation Sevviyadhi chooranam has an optimistic anti-inflammatory activity with more therapeutic value. Conclusion: The study concluded that the Siddha polyherbal formulation Sevviyadhi chooranam has a promising anti-inflammatory activity, probably due to the presence of biologically active phytocompounds. However, it is important to admit that there are some scientific evidences of the potential actions of these phytocompounds in anti-inflammatory activity.

Synthesis, Characterization, and in vitro Anti-Inflammatory Activity of Novel Ferrocenyl(Piperazine-1-Yl)Methanone-based Derivatives.

Inflammation is closely related to the occurrence and development of various diseases in the clinical scope. Finding effective anti-inflammatory agents is of great significance for clinical treatment. A series of novel ferrocenyl(piperazine-1-yl)methanone-based sulfamides and carboxamides were synthesized to discover potent anti-inflammatory agents. The compounds were characterized by 1H NMR, 13C NMR, and MS spectra. Compound 5h was further determined by single crystal X-ray diffraction. All the target compounds were screened for anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW264.7 macrophages. The novel compound (4i) is the preliminary anti-inflammatory mechanism detected by western blot. In a multi-stage screening campaign, compound 4i was shortlisted, which exhibited physicochemical properties suitable for human administration. Among them, compound 4i was found to be most potent in inhibiting NO production (IC50 = 7.65 μM) with low toxicity. This compound also exhibited significant inhibition of the production of iNOS and COX-2. Preliminary mechanism studies indicated that compound 4i could inhibit the activation of the LPS-induced TLR4/NF-κB signaling pathway. The promising anti-inflammatory activity of compound 4i compared with the reference drug suggests that this compound may contribute as a lead compound in the search for new potential anti-inflammatory agents.

Synthesis, anti-inflammatory activity, inverse molecular docking, and acid dissociation constants of new naphthoquinone-thiazole hybrids

Chronic Inflammation is associated with various types of diseases that involves pro-inflammatory cytokines like IL-6 and TNF-α. High costs and serious side effects of available anti-inflammatory/immunomodulatory drugs led us to design new compounds with promising anti-inflammatory activities. Many drugs and biologically important compounds involve naphthoquinone and thiazole moieties in their core structures. Thereby, here we report the synthesis, characterization and anti-inflammatory activities of new naphthoquinone thiazole hybrids by reaction of naphthoquinone acyl thioureas with various α-bromoketone derivatives. The position of NO2 group in one of the phenyl rings of naphthoquinone thiazole hybrids was changed while different substituents were introduced at the para position of the second phenyl ring. All compounds were tested for potential immunomodulatory effect. No inflammatory cytokines were observed in the absence of LPS stimulant. On the other hand, they had promising anti-inflammatory immunomodulatory activities by being able to decrease the production of the pro-inflammatory cytokines (TNF-α and IL-6) in the LPS-stimulated cells. In an effort to find the possible mechanism of action, several enzymes involved in signalling pathways that play critical roles in inflammatory responses were screened in silico. Subsequent to inverse molecular docking approach, PI3K was predicted be the potential target. The docked complexes of the most potent compounds 5g and 5i were subjected to molecular dynamics simulation to assess the binding stability of the igands with the putative target. Acid dissociation constants (pKa) of the products were also determined potentiometrically.

Agarwood oil nanoemulsion counteracts LPS-induced inflammation and oxidative stress in RAW264.7 mouse macrophages

PurposeOxidative stress and inflammation are key pathophysiological features of chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Agarwood oil obtained from Aquilaria trees has promising antioxidant and anti-inflammatory activities. However, its clinical application is hampered by poor solubility. A viable approach to overcome this involves formulation of oily constituents into emulsions. Here, we have investigated the antioxidant and anti-inflammatory potential of an agarwood oil-based nanoemulsion (DE’RAAQSIN) against lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages in vitro. MethodsThe antioxidant and anti-inflammatory activity of DE’RAAQSIN was assessed by measuring the levels of ROS and nitric oxide (NO) produced, using the DCF-DA assay and the Griess reagent assay, respectively. The molecular pathways activated by DE’RAAQSIN were investigated via qPCR. ResultsLPS stimulation of RAW264.7 cells increased the production of nitric oxide (NO) and ROS and resulted in the overexpression of the inducible nitric oxide synthase (iNOS) gene. Furthermore, LPS induced the upregulation of the expression of key proinflammatory genes (IL-6, TNF-α, IL-1β, and CXCL1) and of the antioxidant gene heme oxygenase-1 (HO-1). DE’RAAQSIN demonstrated potent antioxidant and anti-inflammatory activity by significantly reducing the levels of ROS and of secreted NO, simultaneously counteracting the LPS-induced overexpression of iNOS, IL-6, TNF-α, IL-1β, and HO-1. These findings were corroborated by in silico activity prediction and physicochemical analysis of the main agarwood oil components. ConclusionsWe propose DE’RAAQSIN as a promising alternative managing inflammatory disorders, opening the platform for further studies aimed at understanding the effectiveness of DE’RAAQSIN.

Investigation of Anti Inflammatory Activity of Triphala Hydrogels in Carrageenan Induced Paw Edema Model

Inflammation is a reaction of a living vascularized tissue to an injury, conventional or synthetic drugs used in the treatment of inflammatory diseases are inadequate, it sometimes has serious stroke effects. So, number of herbal medicines are recommended for the treatment of inflammation that has no side effects. Hence our study focused to investigate bioactive compounds for anti-inflammatory activity. Folk medicine and ethnopharmacological data can provide a broad range of plants with promising anti-inflammatory activity. Triphala, an ayurvedic formula composed of three different plants. Terminalia chebula Retz., Terminalia bellerica Roxb(Combretaceae) and Phyllanthus emblica L is widely used for various microbial infections. Triphala is now evaluated for its anti-inflammatory action. Triphala is formulated into a hydrogel of different concentrations and is evaluated for in-vitro anti-inflammatory activity by membrane stabilization method at 100, 250 and 500 mg/ml and in-vivo evaluation is done by Carrageenan -induced paw edema method. The results obtained are compared with standard NSAID diclofenac hydrogel. The prepared hydrogel of triphala showed a dose-dependent anti-inflammatory potential in in-vivo and in-vitro methods which provide scientific basis for anti-inflammatory activity of Triphala.

Isolation of curcumin from Lakadong turmeric of Meghalaya and development of its PLGA-Cur-NS loaded nanogel for potential anti-inflammatory and cutaneous wound healing activity in Wistar rats

BackgroundLakadong turmeric (LKD) from Meghalaya, India, boasts high curcumin levels, but lacks scientific study. Moreover, Curcumin's poor solubility hinders its clinical use in inflammation and wound healing. This study isolated curcumin from LKD, forming a PLGA nanosuspension-based nanogel and explored for its potential anti-inflammatory and cutaneous wound healing activity in Wistar rats.MethodologyThe LKD rhizome was successively extracted by soxhlet using chloroform, hexane, ethyl acetate and methanol and their total phenolic content and antioxidant property was determined. Chloroform extract was loaded in column chromatography and curcumin was isolated, purified and characterized by FTIR, NMR, DSC, MS and HPTLC and its purity was analyzed by HPLC. The isolated curcumin was loaded into PLGA nanosuspensions by nanoprecipitation method followed by conversion to carbopol based Nanogel. The nanogels were characterized physicochemically and the drug permeation was observed. The optimized nanogel was evaluated for its anti-inflammatory and cutaneous wound healing activity by carrageenan-induced paw edema and excision wound model in albino Wistar rats divided in five groups and treated with plain carbopol gel, marketed turmeric cream and Cur NS nanogel (0.6% w/w equivalent curcumin each).ResultsResults depicted that the chloroform extract showed the presence of a considerable amount of phenolics with 50-60% yield of curcumin. HPLC analysis depicted that the LKD curcumin had higher purity when compared to standard curcumin. Homogenous curcumin nanosuspensions were obtained with size 150 ± 50 nm and PDI 0.2 ± 0.1. The Cur-NS-nanogel showed satisfactory physical property, drug loading and stability. Ex vivo permeation studies in rats showed controlled permeation with steady state flux of 21.28 ± 0.23 µg/cm2/hr in 24 h. Topical intervention with Cur-NS-nanogel (0.6%) significantly (p < 0.05) decreased the paw volume by 43.97% in the 3rd hour and 72.19% on the 4th hour. Furthermore, the cutaneous wound healing property of Cur-NS-nanogel when compared to negative control rats showed a substantial (p < 0.05) reduction in the percentage wound contraction from 5 to 20th days.ConclusionLKD showed high curcumin content with significant antioxidant effects. LKD curcumin loaded into stable nanogel depicted safe and controlled skin permeability with promising cutaneous wound healing and anti-inflammatory activity in experimental rats.