Anti-osteoarthritic Effects Research Articles

Exploring the mechanism of action of Vanda tessellata extract for the treatment of osteoarthritis through network pharmacology, molecular modelling and experimental assays

The present study employed a comprehensive approach of network pharmacology, molecular dynamic simulation and in-vitro assays to investigate the underlying mechanism of the anti-osteoarthritic potential of Vanda tessellata extract (VTE). Thirteen active compounds of VTE were retrieved from the literature and the IMPPAT database. All of these passed the drug likeness and oral bioavailability parameters. A total of 535 VTE targets and 2577 osteoarthritis related targets were obtained. The compound-target-disease network analysis revealed vanillin, daucosterol, gigantol and syringaldehyde as the core key components. Protein-protein interaction analysis revealed BCL2, FGF2, ICAM 1, MAPK1, MMP1, MMP2, MMP9, COX2, STAT3 and ESR1 as the hub genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed AGE-RAGE signalling pathway, HIF-1 signalling pathway and ESR signalling pathway as the major signalling pathway of VTE involved in treating osteoarthritis. Molecular docking analysis showed daucosterol and gigantol to have good binding affinity with BCL2, ESR1 and MMP9, and the results were further confirmed through molecular dynamics simulation analysis. The mechanism predicted by network pharmacology was validated in vitro on IL-1β-induced SW982 synovial cells. VTE did not show any cytotoxicity and inhibited the migration of SW982 cells. VTE inhibited the expression level of IL-6, IL-8, TNF-α, PGE-2, MMP-2 and MMP-9 in a dose-dependent manner. VTE inhibited nuclear translocation of NF- κβ and suppressed phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) signalling pathway. The results showed that VTE exerted an anti-osteoarthritic effect by a multi-target, multi-component and multi-signalling pathway approach.

Aromatic Plants as Potential Resources to Combat Osteoarthritis.

Osteoarthritis, which affects an estimated 10% of men and 18% of women over the age of 60 and is increasing in genetic prevalence and incidence, is acknowledged as the condition that degrades the quality of life for older adults in the world. There is currently no known treatment for osteoarthritis. The majority of therapeutic methods slow the progression of arthritis or treat its symptoms, making effective treatment to end the degenerative process of arthritis elusive. When non-pharmacological therapy is ineffective, various pharmacological therapies may be used to treat osteoarthritis. Pharmacological therapy, however, can have major adverse effects and be very expensive. As a result, alternative remedies have been researched. The promise for the safe and efficient management of osteoarthritis has been demonstrated by herbal remedies. Experimental research suggests that herbal extracts and compounds can reduce inflammation, inhibit catabolic processes, and promote anabolic processes that are important for treating osteoarthritis. Due to their therapeutic and innate pharmacological qualities, aromatic herbs are frequently employed as herbal remedies. Recent research has shown that aromatic plants have the potency to treat osteoarthritis. Additionally, complex mixtures of essential oils and their bioactive ingredients, which have anti-inflammatory and antioxidant properties and are obtained from aromatic plants, are frequently utilized as complementary therapies for osteoarthritis. To establish new study avenues, the advantageous anti-osteoarthritic effects of aromatic herbal medicines, including plants, essential oils, and their bioactive components, are extensively discussed.

Unlocking the potential of β-1,3-xylooligosaccharides from Caulerpa lentillifera: structural characterization, antioxidative and anti-osteoarthritis applications

Backgroundβ-1,3-Xylooligosaccharides (XOS-3) extracted from Caulerpa lentillifera have shown potential antioxidative and anti-tumor properties, but research on their biological activities, particularly their anti-osteoarthritis effects, is still in early stages.ResultsXOS-3 were produced by eco-friendly enzymatic hydrolysis, displaying a semi-crystalline structure with predominant xylose, xylobiose, xylotriose, and xylotetraose components which were confirmed by IC, SEM, FT-IR, and XRD analysis. Compared with β-1,4-xylooligosaccharides, XOS-3 had stronger antioxidant properties, and the scavenging rate of O2•− and DPPH• radicals was 82.31% and 58.44% at 2.0 mg/mL respectively. In vitro studies, XOS-3 significantly improved cell viability in IL-1β-induced rat chondrocytes from 43.41 to 73.5% at 100 μg/mL, demonstrating anti-inflammatory and cartilage-protective effects by modulating MMP13 and COL2A1 expression.ConclusionsThe study displayed the potential antioxidative and anti-osteoarthritis effects of XOS-3, offering new visuals for the development of marine polysaccharides in the treatment of osteoarthritis.Graphical

Gold nanoparticles exhibit anti-osteoarthritic effects via modulating interaction of the “microbiota-gut-joint” axis

Osteoarthritis (OA) is a common degenerative joint disease that can cause severe pain, motor dysfunction, and even disability. A growing body of research indicates that gut microbiota and their associated metabolites are key players in maintaining bone health and in the progression of OA. Short-chain fatty acids (SCFAs) are a series of active metabolites that widely participate in bone homeostasis. Gold nanoparticles (GNPs) with outstanding anti-bacterial and anti-inflammatory properties, have been demonstrated to ameliorate excessive bone loss during the progression of osteoporosis (OP) and rheumatoid arthritis (RA). However, the protective effects of GNPs on OA progression are not clear. Here, we observed that GNPs significantly alleviated anterior cruciate ligament transection (ACLT)-induced OA in a gut microbiota-dependent manner. 16S rDNA gene sequencing showed that GNPs changed gut microbial diversity and structure, which manifested as an increase in the abundance of Akkermansia and Lactobacillus. Additionally, GNPs increased levels of SCFAs (such as butyric acid), which could have improved bone destruction by reducing the inflammatory response. Notably, GNPs modulated the dynamic balance of M1/M2 macrophages, and increased the serum levels of anti-inflammatory cytokines such as IL-10. To sum up, our study indicated that GNPs exhibited anti-osteoarthritis effects via modulating the interaction of “microbiota-gut-joint” axis, which might provide promising therapeutic strategies for OA.

Structure-Guided Discovery of Potent and Selective CLK2 Inhibitors for the Treatment of Knee Osteoarthritis.

Osteoarthritis is the most common joint disorder. However, there are no disease-modifying drugs approved for OA treatment. CDC2-like kinase 2 (CLK2) could modulate Wnt signaling via alternative splicing of Wnt target genes and further affect bone differentiation, chondrocyte function, and inflammation, making CLK2 an attractive target for OA therapy. In this study, we designed and synthesized a series of highly potent CLK2 inhibitors based on Indazole 1. Among them, compound LQ23 showed more elevated inhibitory activity against CLK2 than the lead compound (IC50, 1.4 nM) with high CLK2/CLK3 selectivity (>70-fold). Furthermore, LQ23 showed outstanding antiosteoarthritis effects in vitro and in vivo, with the roles specific in decreased inflammatory cytokines, downregulated cartilage degradative enzymes, and increased joint cartilage via suppressing CLK2/Wnt signaling pathway. Overall, these data support LQ23 as a potential candidate for intra-articular knee OA therapy, leveraging its unique mechanism of action for targeted treatment.

Network Pharmacology and Experimental Verifications to Discover Scutellaria baicalensis Georgi's Effects on Joint Inflammation, Destruction, and Pain in Osteoarthritis.

Osteoarthritis is the most common type of arthritis, characterized by joint pain and a decline in physiological function. Scutellaria baicalensis Georgi (SB) is potentially effective against osteoarthritis because of its wide range of anti-inflammatory pharmacological activities. This study aimed to identify the mode of action of SB against osteoarthritis using network pharmacology prediction and experimental verification. Networks were constructed to key compounds, hub targets, and pathways essential for SB's effectiveness against osteoarthritis. Additionally, in vivo and in vitro tests were performed, including investigations on weight bearing in hind limbs, the acetic acid-induced writhing response, lipopolysaccharide-stimulated RAW264.7 cells, and serum cytokine responses. We identified 15 active compounds and 14 hub targets, supporting the anti-osteoarthritis effects of SB. The Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that fluid shear stress, atherosclerosis, phosphatidylinositol 3-kinase-Akt signaling, and cellular senescence pathways were important. SB showed substantial anti-inflammatory, analgesic, and joint tissue-protective effects against osteoarthritis. Our study shows that SB has the potential value to be further investigated as a candidate material for the treatment of osteoarthritis in the future.

Anti-osteoarthritis, Bone Protective and Antiinflammatory Effect of Lusianthridin against Monosodium Iodoacetate Induced Osteoarthritis via Suppression of Inflammatory Pathway.

Osteoarthritis (OA) is characterized by the gradual deterioration and worsening of the knee joint, leading to both pain and deformity. The current research exhibited the anti-osteoarthritis effect of lusianthridin against monosodium iodoacetate (MIA) induced OA in rats. RAW cells were used for the cell viability. The inflammatory cytokines and mediators were estimated in the cell lines after the lipopolysaccharide (LPS) treatment. For the in vivo study, the rats were received the intraperitoneal administration of MIA (3 mg/kg) for the induction of OA. The rats were received the oral administration of lusianthridin (5, 10 and 20 mg/kg) and the body and organ weight estimated. Antioxidant, cytokines, inflammatory and matrix metalloproteinases (MMP) level were also estimated. The mRNA expression of MMP were also estimated. The lusianthridin treatment remarkably suppressed the cell viability. LPS induced RAW cell suppressed the level of nitrate, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), prostaglandin (PGE2), MMP-2 and MMP-9 level. Lusianthridin remarkably altered the level of body weight and organ weight (liver, spleen, renal and heart weight). lusianthridin suppressed the oxidative stress via altered the level of antioxidant parameters. Lusianthridin significantly (p < 0.001) decreased the level of cartilage oligometrix matrix protein (COMP) and c-reactive protein (CRP); cytokines such as TNF-α, IL-1β, IL-6, IL-10; inflammatory parameters include 5- Lipoxygenase (5-LOX), COX-2, leukotriene B4 (LTB4), PGE2; transforming growth factor beta (TGF-β); MMP level like MMP-1, 3, 9, 13, respectively. Lusianthridin significantly suppressed the mRNA expression of MMP. Collectively, the result of the study showed that antiosteoarthritis effect of lusianthridin via suppression of inflammatory parameters.

Bone protective effect of sinomenine against monosodium iodoacetate induced knee and hip injury in rat model: an inflammatory pathway.

Osteoarthritis (OA) is a degenerative joint disease which is categorized via destruction of joint cartilage and it also affects the various joints, especially knees and hips. Sinomenine active phytoconstituents isolated from the stem of Sinomenium acutum and already proof anti-inflammatory effect against the arthritis model of rodent. In this experimental protocol, we scrutinized the anti-osteoarthritis effect of sinomenine against monosodium iodoacetate (MIA) induced OA in rats. MIA (3 mg/50 μL) was used for inducing the OA in the rats, and rats received the oral administration of sinomenine (2.5, 5 and 7.5 mg/kg body weight) up to the end of the experimental study (four weeks). The body and organs weight were estimated. Aggrecan, C-terminal cross-linked telopeptide of type II collagen (CTX-II), glycosaminoglycans (GCGs), monocyte chemoattractant protein-1 (MCP-1), Interferon gamma (IFN-γ), antioxidant, inflammatory cytokines, inflammatory mediators and matrix metalloproteinases (MMP) were analyzed. Sinomenine significantly (P < 0.001) boosted the body weight and reduced the heart weight, but the weight of spleen and kidney remain unchanged. Sinomenine significantly (P < 0.001) reduced the level of nitric oxide, MCP-1 and improved the level of aggrecan, IFN-γ and GCGs. Sinomenine remarkably upregulated the level of glutathione, superoxide dismutase and suppressed the level of malonaldehyde. It effectually modulated the level of inflammatory cytokines and inflammatory mediators and significantly (P < 0.001) reduced the level of MMPs, like MMP-1, 2, 3, 9 and 13. Sinomenine is a beneficial active agent for the treatment of OA disease.

Development, optimization, and characterization of rhein loaded nanoemulgel for treatment of osteoarthritis

This work aimed to design a transdermal delivery of rhein loaded nanoemulgel to improve the bioavailability and efficacy of rhein in the treatment of osteoarthritis and reduce its systemic side effects. Rhein loaded nanoemulsion (Rh-NE) prepared by application of ternary phase diagram and spontaneous emulsification method. Box-Behnken design (BBD) was employed to optimize formulation and preparation process of Rh-NE. The optimal formulation was 11.09% mixed oil (rhein and caproyl 90), 22.96% mixed emulsifier (kolliphor RH 40: transcutol HP, 1:1, w/w), and the preparation process was 23.08 min ultrasonic time and 179.5 W ultrasonic power. The particle size of the optimized Rh-NE was 24.5 ± 3.2 nm, PDI was 0.15 ± 0.02, and zeta potential was −18.6 ± 1.8 mV. The Rh-NE was incorporated into hydrogel consisted of 0.85% carbomer, 0.2% poloxamer 188 and 8.0% glycerol to form rhein loaded nanoemulgel (Rh-NE/Gel). In vitro transdermal flux of Rh-NE/Gel was 91.4 ± 0.9 μg/cm2·h. It was found that the inhibition rate of swelling degree of auricle caused by xylene was (54%), inhibition rate of writhing reaction was (60%), percentage increase in pain threshold was (P < 0.01), and the inhibition rate of capillary permeability was (69%). The therapeutic effect of Rh-NE/Gel on osteoarthritis in model rats was significantly improved compared with control group; the swelling degree of joint and toe were significantly reduced by 91% and 71%, respectively, and the contents of inflammatory factors IL-1β and NO were decreased 35.7% and 52.4%, respectively. The developed Rh-NE/Gel could provide anti-osteoarthritis effect and reduce the release of proinflammatory mediators in OA model rats.

Anti-osteoarthritis effects of injectable hyaluronic acid hydrogel loaded with platelet lysate and cerium oxide nanoparticle by regulating TNF-α: An in vitro model

The most prevalent type of joint illness is osteoarthritis, also known as OA. The inflammation of the joint is strongly linked to both the beginning and the progression of osteoarthritis. The use of hydrogels as an OA treatment has the potential to go beyond the administration of anti-inflammatory components to have an inherent immunomodulatory role. Platelet lysate (PL) contains a cocktail of growth factors that actively participates in cartilage repair. Moreover, cerium oxide-nanoparticles (CeO2-NPs) have been broadly studied owing to their powerful antioxidant properties and potential preventive and therapeutic effects against chronic diseases. The current study was designed to determine the effect and mechanism of injectable hyaluronic acid (HA) hydrogel loaded with PL and CeO2-NPs on OA. The results showed that the obtained PL and synthesized CeO2-NPs were effectively incorporated into HA hydrogel and the resultant hydrogel was injectable and have a porous micro structure with interconnected pores. The biological evaluation by qPCR revealed that the fabricated hydrogel exhibited a significantly increased expression of Col2 and Aggrecan (TNF-α-suppressed anabolic molecules) and decreased expression of Col10, Mmp13, Adamts5, and Adamts9 (TNF-α-activated catabolic molecules). Also, ELISA results confirmed this potent antioxidant activity of hydrogel and also increased the growth of chondrocytes over the culturing period.

Anti-Osteoarthritic Effects of Antarctic Krill Oil in Primary Chondrocytes and a Surgical Rat Model of Knee Osteoarthritis.

Osteoarthritis (OA) is characterized by progressive cartilage destruction and synovitis; however, there are no approved disease-modifying OA drugs. Krill oil (KO) has been reported to possess anti-inflammatory properties and alleviate joint pain in knee OA, indicating its potential to target the inflammatory mechanism of OA. Therefore, the anti-OA effects of KO were investigated in primary chondrocytes and a surgical rat model of knee OA. The oral administration of KO at 200 and 100 mg/kg for 8 weeks improved joint swelling and mobility in the animal model and led to increased bone mineral density and compressive strength in the cartilage. The oral KO doses upregulated chondrogenic genes (type 2 collagen, aggrecan, and Sox9), with inhibition of inflammation markers (5-lipoxygenase and prostaglandin E2) and extracellular matrix (ECM)-degrading enzymes (MMP-2 and MMP-9) in the cartilage and synovium. Consistently, KO treatments increased the viability of chondrocytes exposed to interleukin 1α, accompanied by the upregulation of the chondrogenic genes and the inhibition of the ECM-degrading enzymes. Furthermore, KO demonstrated inhibitory effects on lipopolysaccharide-induced chondrocyte inflammation. Histopathological and immunohistochemical analyses revealed that KO improved joint destruction and synovial inflammation, probably due to the anti-inflammatory, anti-apoptotic, and chondrogenic effects. These findings suggest the therapeutic potential of KO for knee OA.

Matrine From Sophora Flavescens Attenuates on Collagen-Induced Osteoarthritis by Modulating the Activity of miR-29B-3P/PGRN Axis.

Matrine is an active ingredient in traditional Chinese medicine that has been shown to be effective in treating bone disorders. The anti-osteoarthritis (OA) effects of matrine were assessed using both in in vitro and in vivo systems, and the mechanisms underlying the effects were investigated by focusing on the activity of miR-29b-3p/PGRN axis. The miR was chosen as potential target for matrine after chondrocytes were treated with both IL-1? and matrine. Changes in cell viability, cell apoptosis, inflammation, and miR-29b-3p/PGRN axis were detected. In vitro assays results were validated using collagen-induced arthritis (CIA) rat models. Incubation with IL-1? reduced cell viability, induced cell apoptosis, and inhibited production of cytokines in chondrocytes, which was associated with the up-regulation of miR-29b-3p and down-regulation of PGRN. In CIA rats, matrine reduced bone destruction and weight loss in a dose-dependent manner. Matrine also reduced the systemic levels of cytokines. At the molecular level, matrine inhibited the expression of miR-29b-3p while increasing the expression of PGRN. The findings outlined in the current study showed that matrine exerted its anti-OA effects by modulating the miR-29b-3p/PGRN axis.

Oxoglaucine Suppresses Hepatic Fibrosis by Inhibiting TGFβ-Induced Smad2 Phosphorylation and ROS Generation

Hepatic fibrosis is the first stage of liver disease, and can progress to a chronic status, such as cirrhosis or hepatocellular carcinoma. Excessive production of extracellular matrix (ECM) components plays an important role in the development of fibrosis. Mechanistically, transforming growth factor beta (TGFβ)-induced phosphorylation of Smad is thought to be a key signaling pathway in the development of liver fibrosis. Although the natural isoquinoline alkaloid oxoglaucine (1,2,9,10-tetramethoxy-7H-dibenzo(de,g)quinolin-7-one) exerts numerous beneficial effects, including anti-cancer, anti-inflammatory, and anti-osteoarthritic effects in diverse cell types, the effects of oxoglaucine on liver fibrosis and fibrogenic gene expression have not been fully elucidated. The aim of this study is to evaluate the signaling pathway and antifibrotic activity of isoquinoline alkaloid oxoglaucine in TFGβ-induced hepatic fibrosis in vitro. Using Hepa1c1c7 cells and primary hepatocytes, we demonstrated that oxoglaucine treatment resulted in inhibition of the expression of fibrosis markers such as collagen, fibronectin, and alpha-SMA. Subsequent experiments showed that oxoglaucine suppressed TGFβ-induced phosphorylation of Smad2 and reactive oxygen species (ROS) generation, without altering cell proliferation. We further determined that the increase in Smad7 by oxoglaucine treatment is responsible for the inhibition of Smad2 phosphorylation and the anti-fibrogenic effects. These findings indicate that oxoglaucine plays a crucial role in suppression of fibrosis in hepatocytes, thereby making it a potential drug candidate for treatment of liver fibrosis.

Siraitia grosvenorii Residual Extract Inhibits Inflammation in RAW264.7 Macrophages and Attenuates Osteoarthritis Progression in a Rat Model.

Osteoarthritis (OA) is a degenerative joint disease characterised by cartilage degeneration and chondrocyte inflammation. We investigated the anti-inflammatory effects of the Siraitia grosvenorii residual extract (SGRE) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages in vitro and its anti-osteoarthritic effects in a monosodium iodoacetate (MIA)-induced OA rat model. SGRE dose-dependently decreased nitric oxide (NO) production in LPS-induced RAW264.7 cells. Moreover, SGRE reduced the pro-inflammatory mediator (cyclooxygenase-2 (COX2), inducible NO synthase (iNOS), and prostaglandin E2 (PGE2)) and pro-inflammatory cytokine (interleukin-(IL)-1β, IL-6, and tumour necrosis factor (TNF-α)) levels. SGRE suppressed nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway activation in RAW264.7 macrophages, thus reducing inflammation. Rats were orally administered SGRE (150 or 200 mg/kg) or the positive control drug JOINS (20 mg/kg) 3 days before MIA injection, and once daily for 21 days thereafter. SGRE elevated the hind paw weight-bearing distribution, thus relieving pain. It also reduced inflammation by inhibiting inflammatory mediator (iNOS, COX-2, 5-LOX, PGE2, and LTB4) and cytokine (IL-1β, IL-6, and TNF-α) expression, downregulating cartilage-degrading enzymes, such as MMP-1, -2, -9, and -13. SGRE significantly reduced the SOX9 and extracellular matrix component (ACAN and COL2A1) levels. Therefore, SGRE is a potential therapeutic active agent against inflammation and OA.

Protective Effects of Glycine soja Leaf and Stem Extract against Chondrocyte Inflammation and Osteoarthritis.

Wild soybean, also known as Glycine soja Sieb. et Zucc. (GS), has long been known for its various health benefits. Although various pharmacological effects of G. soja have been studied, the effects of GS leaf and stem (GSLS) on osteoarthritis (OA) have not been evaluated. Here, we examined the anti-inflammatory effects of GSLS in interleukin-1β (IL-1β)-stimulated SW1353 human chondrocytes. GSLS inhibited the expression of inflammatory cytokines and matrix metalloproteinases and ameliorated the degradation of collagen type II in IL-1β-stimulated chondrocytes. Furthermore, GSLS played a protective role in chondrocytes by inhibiting the activation of NF-κB. In addition, our in vivo study demonstrated that GSLS ameliorated pain and reversed cartilage degeneration in joints by inhibiting inflammatory responses in a monosodium iodoacetate (MIA)-induced OA rat model. GSLS remarkably reduced the MIA-induced OA symptoms, such as joint pain, and decreased the serum levels of proinflammatory mediators, cytokines, and matrix metalloproteinases (MMPs). Our findings show that GSLS exerts anti-osteoarthritic effects and reduces pain and cartilage degeneration by downregulating inflammation, suggesting that it is a useful therapeutic candidate for OA.

Total lignans from Vitex negundo seeds attenuate osteoarthritis and their main component vitedoin A alleviates osteoclast differentiation by suppressing ERK/NFATc1 signaling.

The seeds of Vitex negundo have been used for inflammation-related disease treatment in traditional medicine. This study focused on the anti-osteoarthritis (OA) effects of the total lignans of V. negundo seeds (TOV) in monosodium iodoacetate-induced osteoarthritis rats and its pharmacokinetic properties, as well as the effects and potential mechanism of its main components VN1 (6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydro-xymethyl-7-methoxy-3,4-dihydro-2-naphthaldehydeb) and VN2 (vitedoin A) on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs). TOV significantly attenuated osteoarthritis, leading to an increase in pain thresholds, improvement of knee articular cartilages and chondrocytes loss, and decreased total joint scores and serum levels of TNF-α, interleukin-1β (IL-1β), and prostaglandin E2 (PGE2) in osteoarthritis rats. The half-time (T1/2 ) was 2.82 h and 1.33 h, and the bioavailability was 15.34%-21.89% and 16.29%-22.11%, for VN1 and VN2, respectively. VN2, rather than VN1, remarkably inhibited tartrate-resistant acid phosphatase (TRAP) activity, reduced the number of TRAP-positive multinuclear cells, diminished the formation of actin ring, and decreased mRNA levels of cathepsin K (CTSK), TRAP, nuclear factor of activated T cell 1 (NFATc1), and osteoclast-associated receptor, as well as downregulated protein levels of p-ERK (phosphorylated extracellular signal-regulated kinase), TRAP, CTSK and NFATc1 in BMMs. These findings suggest TOV has promising therapeutic potential for OA treatment and VN2, in particular, attenuates osteoclast differentiation by suppressing ERK/NFATc1 signaling and actin ring, mainly accounting for the anti-OA efficacy of TOV.

Anti-Osteoarthritic Effects of Prunella Vulgaris and Gentiana Lutea In Vitro and In Vivo.

Osteoarthritis (OA) is the progressive destruction of articular cartilage with severe symptoms, including pain and stiffness. We investigated the anti-osteoarthritic effects of Prunella vulgaris (PV) and Gentiana lutea (GL) extract in primary cultured chondrocytes RAW 264.7 cells in vitro and destabilization of the medial meniscus (DMM)-induced OA mice in vivo. Primary chondrocytes were induced with IL-1β, and RAW 264.7 cells were treated with LPS and co-incubated with either individual extracts of PV and GL or different ratios of PV and GL mixture. For the OA animal model, the medial meniscus (DMM) was destabilized in 9-week-old male C57BL/6 mice. Treatment of individual PV and GL and combination of PV and GL extracts inhibited the mRNA expression level of COX2 in chondrocytes and RAW 264.7 cells. The optimized inhibitory effect was attained with a PV and GL combination at an 8:2 ratio (PG) without cytotoxic effects. PG extracts prevented the expression of catabolic factors (COX2, Mmp3, Mmp9, and Mmp13) and inflammatory mediator levels (PGE2 and collagenase). In addition, PG decreased subchondral sclerosis and increased BMD in the subchondral region of DMM-induced OA mice with protection of articular cartilage destruction by inhibiting inflammatory processes. This study suggests that PG may be an alternative medicinal herb for treatment of OA.

12-Epi-Napelline regulated TGF-β/BMP signaling pathway mediated by BMSCs paracrine acceleration against osteoarthritis

BackgroundThis study is to investigate the role of 12-Epi-Napelline, a new alkaloid isolated from aconitum, in promoting the paracrine of Bone Mesenchymal Stem Cells (BMSCs) and the synergistic therapeutic effects on osteoarthritis. MethodWe tested the cytotoxicity and optimization of 12-Epi-Napelline, and then simulated the osteoarthritis model in vitro damaging the chondrocytes by lipopolysaccharide (LPS) and RT-qPCR, Western blot and Immunofluorescence were used to detect the inflammatory factor IL-1β, COX-2, TNF-α, MMP-13 and anabolic cytokines of Col-2, BMP-2, TGF-β1 and Sox9 expression in chondrocytes after 12-Epi-Napelline treatment. Under the treatment of different time, Col-2, BMP-2, TGF-β1 and Sox9 expression in BMSCs were detected by RT-qPCR, Western blot, and Immunofluorescence. By establishing an osteoarthritis model in vivo, the anti-osteoarthritis effect of 12-Epi-Napelline or BMSCs was evaluated. ResultsThe results showed the expressions of IL-1β, COX-2, TNF-α, and MMP-13 were down-regulated in chondrocytes after 12-Epi-Napelline treatment, while the expression of Col-2, BMP-2, TGF-β1 and Sox9 were increased to normal chondrocytes. These increased expression also occurred in BMSCs. BMSCs had the trend of transforming into chondrocytes by regulating TGF-β signaling pathway under the treatment of 12-Epi-Napelline. ConclusionThis study could confirm that 12-Epi-Napelline is not only effective in the treatment of osteoarthritis, but also can induce BMSCs to secrete growth factors that promote chondrocyte repair to help repair the damage caused by osteoarthritis.

The Xiaogu San Attenuates Pain and Cartilage Damage in Rats with Monosodium Iodoacetate Induced Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease with an increasing incidence associated with increased life expectancy. The application of traditional Chinese medicine in the treatment of OA has become a research hotspot. This study investigated the effects of XGS externally applied to osteoarthritic joints and analyze its effect on pain in monosodium iodoacetate (MIA)-induced OA rats. This study also evaluates potential mechanisms behind the anti-osteoarthritic effects of XGS. A total of 24 Sprague Dawley rats were evenly and randomly divided into three separate groups, including the normal control (NC), OA and XGS groups. MIA (50 μL, 10 mg/mL) was injected into the left knee joints of the rats to induce OA. After 7 days, The rats of XGS group were given XGS (0.45 g) that was externally applied to the left knee joint, were fixed with gauze, and continuously administered XGS for 28 days. Morphological changes in tissues and organs were examined using H&E staining. Biochemical indicators were measured using an automatic biochemical analyzer. Inflammatory cytokines were detected using ELISA kits and immunohistochemistry. RNA-based high-throughput sequencing (RNA-seq) was performed to detect differential expression of mRNAs in normal and MIA-induced OA rats. Stride of the left leg was extended in rats, matrix increased on cartilage tissue surfaces, and inflammatory cytokines were reduced when treated with XGS. RNA-seq results revealed that the PI3K-Akt signaling pathway is activated in the OA model. The qRT-PCR showed that the expression levels of Tnn, Col6a6, Igf1 and Lamb1 were up-regulated by XGS. Altogether, this work demonstrated the potential therapeutic effects of XGS in rats with OA induced by MIA. The XGS may be considered an alternative therapy to manage OA.

Crataegus sinaica defatted methanolic extract ameliorated monosodium iodoacetate-induced oxidative stress andinhibited inflammation in a rat model of osteoarthritis.

Osteoarthritis is a degenerative joint disease without definite treatment. It is characterized by intra-articular inflammation, cartilage degeneration, subchondral bone remodeling, and joint pain. The objective of the current study was to assess the anti-osteoarthritic effect and the possible underlying mechanism of action of Crataegus sinaica extract (CSE). Intra-articular injection of monosodium iodoacetate in the right knee joint of all rats was done except for the sham group. One week later, the anti-inflammatory efficacy of CSE (100, 200, 300 mg/kg, daily p.o) for 4 successive weeks versus ibuprofen (40 mg/kg, p.o) was assessed. Serum inflammatory cytokines; as well as weekly assessment of knee joint swelling, joint mobility, and motor coordination were done. At the end of the experiment, a histopathological investigation of the affected knee joints and an x-ray investigation were also executed. CSE significantly decreased joint swelling, pain behaviors, and serum levels of TNF-α, IL6, hyaluronic acid, and CTX-II. The radiographic findings revealed almost normal joint space with normal radiodensity and diameter in CSE-treated rats. As well, the histopathological and immunohistochemical investigations of the knee joints in CSE-treated groups retained the cartilage structure of knee joints. A significant reduction in the percentage of caspase-3-stained chondrocytes and a decrease in TGF-β1 immuno-positive areas in the synovial lining and sub lining were recorded in CSE-treated rats, compared to the osteoarthritis control group. This study approved the chondroprotective effects of CSE, and its ability to inhibit the pain associated with osteoarthritis.