Network pharmacology combined with experimental validation to investigate the effect of Rongjin Niantong Fang on chondrocyte apoptosis in knee osteoarthritis.

Knee osteoarthritis (KOA) is a chronic degenerative disease that affects the quality of life of middle­aged and elderly individuals, and is one of the major factors leading to disability. Rongjin Niantong Fang (RJNTF) can alleviate the clinical symptoms of patients with KOA, but the molecular mechanism underlying its beneficial effects on KOA remains unknown. Using pharmacological analysis and in vitro experiments, the active components of RJNTF were analyzed to explore their potential therapeutic targets and mechanisms in KOA. The potential targets and core signaling pathways by which RJNTF exerts its effects on KOA were obtained from databases such as Gene Expression Omnibus, Traditional Chinese Medicine Systems Pharmacology and Analysis Platform. Subsequently, chondrocyte apoptosis was modeled using hydrogen peroxide (H2O2). Cell Counting Kit­8 assay involving a poly [ADP­ribose] polymerase­1 (PARP1) inhibitor, DAPI staining, reverse transcription­quantitative PCR, Annexin V­FITC/PI staining and flow cytometry, western blotting and co­immunoprecipitation analysis were used to determine the therapeutic efficacy of RJNTF on KOA and to uncover the molecular mechanism. It was found that PARP1­knockdown lentivirus, incubation with PARP1 inhibitor PJ34, medium and high doses of RJNTF significantly reduced H2O2­induced chondrocyte apoptosis. Medium and high doses of RJNTF downregulated the expression of cleaved caspase­3, cleaved PARP1 and PAR total proteins, as well as nucleus proteins of apoptosis­inducing factor (AIF) and migration inhibitory factor (MIF), and upregulated the expression of caspase­3, PARP1 total protein, as well as the cytoplasmic expression of AIF and MIF, suggesting that RJNTF may inhibit chondrocyte apoptosis through the PARP1/AIF signaling pathway.

[Status of outcome measures in randomized controlled trials of kidney-tonifying and blood-activating method in treatment of knee osteoarthritis].

This study assesses the status of outcome measures in the randomized controlled trial(RCT) involving the kidney-tonif-ying and blood-activating method for treating knee osteoarthritis(KOA), aiming to establish a theoretical foundation for the development of a core set of outcome measures in traditional Chinese medicine(TCM) treatment of KOA. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, in addition to ClinicalTrials.gov and the China Clinical Trial Registration Center, with the time interval from inception to August 2023. The RCT of treating KOA with the kidney-tonifying and blood-activating method was included. Two assessors independently conducted literature screening, data collection, and qualitative analysis to compile the outcome measure results. A total of 350 RCTs were included, involving 165 outcome measures with the total frequency of 1 462. These outcome measures were categorized into six domains: symptom and sign measures(23) with the frequency of 718(49.1%), TCM symptom and syndrome measures(3) with the frequency of 53(3.6%), physical examination measures(130) with the frequency of 506(34.6%), quality of life measures(4) with the frequency of 20(1.3%), long-term efficacy measures(2) with the frequency of 6(0.4%), and safety measures(3) with the frequency of 159(10.9%). Additionally, 53 studies used TCM syndrome and symptom scores as indicators of efficacy, employing eight distinct measurement tools. The RCTs involving the kidney-tonifying and blood-activating method for treating KOA had a variety of problems, such as unclear prio-ritization of outcome measures, diversity in measurement tools, absence of standardized assessment criteria for specific measures, and non-standardized usage. These problems affected the research quality and reliability. Hence, it is advisable to draw upon international expertise, improve research design, and merge TCM efficacy characteristics with clinical research to establish a core set of KOA outcome measures aligned with TCM principles.

Miao medicine Gu Yan Xiao tincture inhibits mTOR to stimulate chondrocyte autophagy in a rabbit model of osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Gu Yan Xiao tincture, a blend of traditional Chinese herbs, is traditionally used for osteoarthritis and related pain. This study investigated its mechanism of action in order to rationalize and validate its therapeutic use. AIM OF THE STUDY: This study analyzed, in a rabbit model of knee osteoarthritis, whether and how Gu Yan Xiao tincture exerts therapeutic benefits by modulating chondrocyte autophagy. MATERIALS AND METHODS: The active constituents within the GYX tincture were identified using liquid chromatography-mass spectrometry. The rabbit model was established by injecting animals with type II collagenase intra-articularly, and the effects of topically applied tincture were examined on osteoarthritis lesions of the knee using histopathology, micro-computed tomography and x-ray imaging. Effects of the tincture were also evaluated on levels of inflammatory cytokines, matrix metalloproteases, and autophagy in chondrocytes. As a positive control, animals were treated with sodium diclofenac. RESULTS: The tincture mitigated the reduction in joint space, hyperplasia of the synovium and matrix metalloproteases in serum that occurred after injection of type II collagenase in rabbits. These therapeutic effects were associated with inhibition of mTOR and activation of autophagy in articular chondrocytes. Inhibiting mTOR with rapamycin potentiated the therapeutic effects of the tincture, while inhibiting autophagy with 3-methyladenine antagonized them. CONCLUSIONS: Gu Yan Xiao tincture mitigates tissue injury in a rabbit model of osteoarthritis, at least in part by inhibiting mTOR and thereby promoting autophagy in chondrocytes. These results rationalize the use of the tincture not only against osteoarthritis but also potentially other diseases involving inhibition of autophagy in bones and joints.

Efficacy and safety of extracorporeal shock wave therapy combined with sodium hyaluronate in treatment of knee osteoarthritis: a systematic review and Meta-analysis.

OBJECTIVE: To assess the efficacy and safety of extracorporeal shockwave therapy (ESWT) combined with sodium hyaluronate (HA) for the treatment of knee osteoarthritis (KOA). METHODS: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database, and SinoMed were searched from inception to July 2020. The quality of the randomized controlled trials was evaluated independently by two reviewers according to the criteria in the Cochrane Collaboration for Systematic Reviews. The identified articles were then screened individually using EndnoteX9 for eligibility in this Meta-analysis. The heterogeneity among the articles was evaluated using I2. RESULTS: A total of 17 studies, comprising 2000 individuals, were included in this Meta-analysis. The results showed that a significant improvement was observed in knee pain and function based on the clinical efficacy of ESWT combined with HA. Statistical analysis of clinical efficacy showed that [relative risk (RR) = 1.21, 95% confidence interval (CI) (1.12, 1.30), P < 0.01]. Statistical analysis of visual analog scale showed that [standardized mean difference (SMD) = －2.84, 95%CI (－4.01, －1.66), P < 0.01]. Western Ontario and McMaster University osteoarthritis index statistical analysis showed that [SMD = －1.57, 95% CI (－2.52, －0.61), P < 0.01]. Lysholm score statistical analysis showed that [SMD = 1.71, 95% CI (0.98, 2.44), P < 0.01]. In addition, only minor side effects, such as redness and swelling of the skin, were observed. CONCLUSIONS: Medium to low quality evidence showed that ESWT combined with HA offers an inexpensive, well-tolerated, safe, and effective method to improve pain and functionality in patients with KOA. However, tightly controlled, randomized, large multicenter trials are warranted to validate the current findings.

Effectiveness of Bach Nien Kien Health Supplement in the Treatment of Patients With Symptomatic Knee Osteoarthritis.

BACKGROUND/AIM: Knee osteoarthritis (KOA) is the most common disease in adults. We conducted a clinical study to evaluate the efficacy and safety of Bach Nien Kien (BNK) in supportive therapy for patients with symptomatic KOA. PATIENTS AND METHODS: An open interventional study was performed on 60 patients aged 38 to 70 with the diagnosis of symptomatic KOA. The patients were assigned to a study group (SG) with 30 subjects and a control group (CG) with 30 subjects using a matching method. The patients in SG were treated with electroacupuncture, glucosamine supplement, and BNK, while the patients in CG received the same treatment without BNK. RESULTS: At the end of the 30-day treatment (d30), the SG had a reduction in VAS score compared to a pre-treatment level of 3.03±0.96 points, which was more than the CG of 2.5±0.90 points. The excellent result in the SG was 10%, and the CG had no excellent result. The good result in the SG was 56.7%, and the CG group was only 26.7%. The moderate and poor results in the CG were high, 63.3%, and 10%, respectively; in the SG, only 26.7% and 6.7%. The difference in overall treatment results between the SG and CG was statistically significant (p<0.05). During the 30-day treatment period in both groups, no patient reported any undesirable effects. CONCLUSION: Bach Nien Kien health supplement is effective and safe for controlling KOA symptoms and improving joint motion and quality of life for patients with symptomatic KOA.

Knee osteoarthritis: A review of animal models and intervention of traditional Chinese medicine.

BACKGROUND: Knee osteoarthritis (KOA) characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults. The pathophysiology of KOA remains poorly understood, as it involves complex mechanisms that result in the same outcome. Consequently, researchers are interested in studying KOA and require appropriate animal models for basic research. Chinese herbal compounds, which consist of multiple herbs with diverse pharmacological properties, possess characteristics such as multicomponent, multipathway, and multitarget effects. The potential benefits in the treatment of KOA continue to attract attention. PURPOSE: This study aims to provide a comprehensive overview of the advantages, limitations, and specific considerations in selecting different species and methods for KOA animal models. This will help researchers make informed decisions when choosing an animal model. METHODS: Online academic databases (e.g., PubMed, Google Scholar, Web of Science, and CNKI) were searched using the search terms "knee osteoarthritis," "animal models," "traditional Chinese medicine," and their combinations, primarily including KOA studies published from 2010 to 2023. RESULTS: Based on literature retrieval, this review provides a comprehensive overview of the methods of establishing KOA animal models; introduces the current status of advantages and disadvantages of various animal models, including mice, rats, rabbits, dogs, and sheep/goats; and presents the current status of methods used to establish KOA animal models. CONCLUSION: This study provides a review of the animal models used in recent KOA research, discusses the common modeling methods, and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Periostial and cartilage morphology in knee osteoarthritis: beneficial effects of supplementation with Pycnogenol® + Centellicum®.

BACKGROUND: The aim of this registry study was to evaluate the progress of osteoarthrosis (OA) symptoms after the intake of a new standardized supplement combination (Pycnogenol® + Centellicum®, both Horphag Research) in a group of subjects with OA. METHODS: Supplemented subjects took daily 150 mg Pycnogenol® + 450 mg Centellicum® for 6 months. Another comparable group of subjects using only standard management (SM) was included as a reference. RESULTS: Forty-five subjects with a mean age of 42 years completed the study, 25 in the supplemented group and 20 in the SM group. There were no safety problems or tolerability issues with the supplements. The two groups, SM and SM + Pycnogenol® + Centellicum® were comparable for age and clinical characteristics at inclusion. The two main ultrasound characteristics of cartilage, its thickness and surface-irregularity were more improved with the supplements. Pain scores, C reactive protein, the level of fitness and the use of extra pain killers (as rescue medication) were all significantly improved at 6 months with the supplement combination compared to SM (P<0.05). Plasma free radicals, pain-free walking distance on treadmill and erythrocyte sedimentation rate (ESR) were significantly improved with the supplements compared to SM. CONCLUSIONS: The morphological improvement - visible with ultrasound - correlates with a decrease in clinical symptoms and with a more efficient ambulation without pain. SM along with the Pycnogenol® Centellicum® combination are useful to avoid drug treatments that may expose patients to some side effects over time.

Open, Observational, Single-Arm, Multicenter Study Assessing the Effectiveness of a Dietary Supplement Containing Hydrolyzed Collagen, Chondroitin Sulfate, and Glucosamine for Osteoarthritis Pain Reduction.

Osteoarthritis (OA) is an age-related degenerative joint disease with a great impact on patients' well-being and quality of life. This is an observational, open, single-arm multicenter study aimed to evaluate the effectiveness of a nutritional supplement in patients with knee and/or hip OA. A total of 186 patients were recruited from Spanish centers and received a supplement containing hydrolyzed collagen (3000 mg), chondroitin sulfate (800 mg), glucosamine sulfate (700 mg), turmeric extract (250 mg) and devil's claw (150 mg), once daily during 6 months. The primary outcome was the patients' self-perceived pain in the affected joints measured with a visual analogue scale (VAS). Secondary outcome was the patient's functioning, measured with the Lequesne Functional Index and the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Participants showed a significant reduction in self-perceived pain after 3 (mean reduction ± standard deviation, 1.99 ± 1.05) and 6 months (3.57 ± 1.39) of treatment (p < 0.0001 in both comparisons). Lequesne Functional Index score was significantly reduced at 3 months (3.86 ± 2.94) and at 6 months (6.73 ± 4.30) of treatment (p < 0.0001 in both comparisons). The WOMAC index was also significantly reduced after 3 (14.24 ± 10.04) and 6 months (26.43 ± 17.35) of treatment (p < 0.0001 in both comparisons). Significant reductions in WOMAC subdomains (p < 0.0001 in all comparisons) were observed. No severe adverse events were reported during the study. The main results arising from this study show that this nutritional supplementation can improve OA-related symptoms and physical function with a good safety profile in patients with hip and/or knee OA.

American Academy of Orthopaedic Surgeons Technology Overview Summary: Platelet-Rich Plasma (PRP) for Knee Osteoarthritis.

The Platelet-Rich Plasma (PRP) for Knee Osteoarthritis Technology Overview is based on a systematic review of current scientific and clinical research. Through analysis of the current best evidence, this technology overview seeks to evaluate the efficacy of PRP for patients with knee osteoarthritis. The systematic literature review resulted in 54 articles: 36 high-quality and 18 moderate-quality. The findings of these studies were summarized to present findings on PRP versus control/placebo, acetaminophen, non-steroidal anti-inflammatory drugs, corticosteroids, exercise, prolotherapy, autologous conditioned serum, bone marrow aspirate concentrate, hyaluronic acid, and ozone therapy. In addition, the work group highlighted areas that needed additional research when evidence proved lacking on the topic and carefully noted the potential harms associated with an intervention, required resource utilization, acceptability, and feasibility.

The Effect of St. John's Wort Oil (Hypericum Perforatum L.) in Knee Osteoarthritis: A Randomized Controlled and Qualitative Study.

BACKGROUND: Reducing pain and improving physical function are critical in the treatment of osteoarthritis. Although individuals use St. John's Wort oil to relieve pain due to osteoarthritis, no scientific research has been found investigating its effectiveness. AIM: This study investigated the effect of St. John's Wort oil on pain intensity and physical functions in people with knee osteoarthritis. METHODS: This study adopted a single-blind, randomized, placebo-controlled, and qualitative mixed design. The sample consisted of 60 patients randomized into intervention (n = 30) and placebo control (n=30) groups. The experimental group participants were treated with topically St. John's Wort oil three times a week for 3 weeks, and the placebo control group participants were treated with olive oil three times a week for 3 weeks. Quantitative data were collected using a patient identification form, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Visual Analogue Scale. Qualitative data were collected through semi-structured interviews. RESULTS: The experimental group had a significantly lower mean Visual Analog Scale score in the first, third, and fourth follow-ups than the control group. The experimental group had significantly lower mean WOMAC-pain, WOMAC-stiffness, and WOMAC-physical function subscale scores in the last follow-up than in the first follow-up. The qualitative data agreed with the quantitative data. CONCLUSIONS: The results show that St. John's Wort oil helps people with knee osteoarthritis feel less pain and become physically more active. Additional research is warranted to better understand the effect of St. John's Wort oil on pain intensity and physical functions in people with knee osteoarthritis.

Confirmation of pain-related neuromodulation mechanism of Bushen Zhuangjin Decoction on knee osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Zhuangjin Decoction (BZD) are an herbal compound commonly used to treat osteoarthritis (OA) in China. AIM OF THE STUDY: This study aimed to verify the mechanism of Bushen Zhuangjin Decoction in relieving the pain of knee osteoarthritis. MATERIALS AND METHODS: Network pharmacology evaluation was used to discover the potential targets of BZD to relieve pain in KOA. The therapeutic effects of BZD treatment on KOA pain using histomorphology, behavioral assessments, suspension chip analysis, and ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) assays. The functional magnetic resonance imaging was used to explore the effects of BZD treatment on brain function associated to KOA. RESULTS: Network pharmacological analysis revealed the association between the analgesic effect of BZD on KOA and the pain signaling neurotransmitter 5-HT. Subsequently, we conducted experiments to verify the therapeutic effect of BZD on pain in KOA animal models. Behavioral tests demonstrated that the pain threshold of knee osteoarthritis rats decreased in PWT and PWL, but BZD was able to increase the pain threshold. Histopathological staining indicated thinning of the cartilage layer and sparse trabeculae in the subchondral bone. Suspension chip analysis revealed a significant increase in pro-inflammatory factors of IL-1α, IL-5, IL-12, IL-17A, RANTES, TNF-α and M-CSF in KOA, along with a significant decrease in anti-inflammatory factor of IL-13. However, BZD treatment decreased the expression of pro-inflammatory factors and increased the content of anti-inflammatory factor. UHPLC-MS/MS analysis showed a significant decrease in the serum levels of GABA, E, GSH, Kyn, Met, and VMA in KOA, which were significantly increased by BZD. Conversely, the serum levels of TrpA, TyrA, Spd, and BALa were significantly increased in KOA and significantly decreased by BZD. ELISA and Western blot analysis showed increased expression of subchondral bone pain-related neuropeptides SP, CGRP, TH, NPY, VEGFA, 5-HT3 in KOA, which were decreased in BZD. Functional magnetic resonance imaging demonstrated that BZD exerts its therapeutic effect on KOA by modulating the activity and functional connections of the cortex, hypothalamus, and hippocampus. CONCLUSIONS: This study confirmed the significant role of pain-related neuromodulation mechanisms in the analgesic therapy of BZD and provides a theoretical foundation for using BZD as a traditional Chinese medical treatment for KOA pain.

Danggui-Shaoyao-San (DSS) ameliorates the progression of osteoarthritis via suppressing the NF-κB signaling pathway: an in vitro and in vivo study combined with bioinformatics analysis.

BACKGROUND: Osteoarthritis (OA) is a common chronic age-related joint disease characterized primarily by inflammation of synovial membrane and degeneration of articular cartilage. Accumulating evidence has demonstrated that Danggui-Shaoyao-San (DSS) exerts significant anti-inflammatory effects, suggesting that it may play an important role in the treatment of knee osteoarthritis (KOA). METHODS: In the present study, DSS was prepared and analyzed by high-performance liquid chromatography (HPLC). Bioinformatics analyses were carried out to uncover the functions and possible molecular mechanisms by which DSS against KOA. Furthermore, the protective effects of DSS on lipopolysaccharide (LPS)-induced rat chondrocytes and cartilage degeneration in a rat OA model were investigated in vivo and in vitro. RESULTS: In total, 114 targets of DSS were identified, of which 60 candidate targets were related to KOA. The target enrichment analysis suggested that the NF-κB signaling pathway may be an effective mechanism of DSS. In vitro, we found that DSS significantly inhibited LPS-induced upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP3), and matrix metalloproteinase-13 (MMP13). Meanwhile, the degradation of collagen II was also reversed by DSS. Mechanistically, DSS dramatically suppressed LPS-induced activation of the nuclear factor kappa B (NF-κB) signaling pathway. In vivo, DSS treatment prevented cartilage degeneration in a rat OA model. CONCLUSIONS: DSS could ameliorate the progression of OA through suppressing the NF-κB signaling pathway. Our findings indicate that DSS may be a promising therapeutic approach for the treatment of KOA.

Efficacy of Herbal Medicine in Hand Osteoarthritis: A Narrative Review.

OBJECTIVE: Osteoarthritis (OA) is one of the most prevalent joint disorders in the world that has placed an enormous economic and social burden on governments and healthcare sectors in many countries. Hand OA (HOA) is the most common peripheral arthritis, which is less investigated than knee and hip OA. Due to limited approved drug choices and adverse effects of long-term use of current regimens, we aimed to review the existing evidence that were used as oral herbal medicine to treat HOA. METHODS: The PubMed database was searched for both observational and interventional studies that have investigated herbal medicine safety and efficacy in HOA, written in English and published between 2010 and 2022. RESULTS: A total of 5 original articles fulfilled the inclusion criteria, and each article assessed a different herbal regimen. Overall, it seems desirable to add specific herbal treatments to the regimen of HOA patients, specifically in case of early stages of HOA. CONCLUSION: Currently, the need for a low-risk alternative treatment in HOA patients is felt more than ever. There are reliable references relating to the safety of Korean red ginseng, GCSB-5, XLGB, and GS-GCu in these patients, although their efficacy was limited. Additionally, herbs like curcumin and Boswellia serrata have positively affected patients with knee osteoarthritis. However, there is a lack of strong evidence supporting their effectiveness in hand osteoarthritis (HOA). This emphasizes the potential benefits that these herbs may have for HOA patients.

Efficacy and safety of curcumin therapy for knee osteoarthritis: A Bayesian network meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumin, a polyphenolic compound extracted from turmeric (Curcuma longa L.), is widely used in traditional Chinese medicine to treat osteoarthritis and rheumatoid arthritis. Clinical and experimental studies show that curcuminoid formulations have considerable clinical application value in the treatment of knee osteoarthritis (KOA). AIM OF THE STUDY: To evaluate the efficacy and safety of curcumin, both alone and in combination with other drugs, in KOA treatment through a Bayesian network meta-analysis (NMA). METHODS: We searched PubMed, Embase and Cochrane Library for randomized controlled trials of curcumin for KOA treatment. The time range of the search was from the establishment of each database to April 26, 2023. The NMAs of outcome indicators were all performed using a random-effects model. NMAs were calculated and graphed in R using MetaInsight and Stata 140 software. Measurement data were represented by the mean difference (MD), while count data were represented by the odds ratio (OR); the 95% confidence interval (CI) of each effect size was also calculated. RESULTS: This study included 23 studies from 7 countries, including 2175 KOA patients and 6 interventions. The NMA results showed that compared with placebo, curcumin significantly reduced the visual analogue scale pain score (MD = -1.63, 95% CI: -2.91 to -0.45) and total WOMAC score (MD = -18.85, 95% CI: -29.53 to -8.76). Compared with placebo, curcumin (OR = 0.17, 95% CI: 0.08 to 0.36), curcumin + NSAIDs (OR = 0.01, 95% CI: 0.00 to 0.13) and NSAIDs (OR = 0.11, 95% CI: 0.02 to 0.47) reduced the use of rescue medication. Compared with NSAIDs, curcumin (OR = 0.51, 95% CI: 0.25 to 0.94) and curcumin + NSAIDs (OR = 0.23, 95% CI: 0.06 to 0.9) had a reduced incidence of adverse reactions. The surface under the cumulative ranking curve results indicated that curcumin monotherapy, curcumin + chondroprotective agents, and curcumin + NSAIDs have good clinical value in KOA treatment. CONCLUSIONS: Curcumin, either alone or in combination with other treatments, is considered to have good clinical efficacy and safety in KOA treatment. Drug combinations containing curcumin may have the dual effect of enhancing efficacy and reducing adverse reactions, but this possibility still needs to be confirmed by further clinical and basic research.

Study of the curative effect of Zhang's Xibi formula and its underlying mechanism involving inhibition of inflammatory responses and delay of knee osteoarthritis.

OBJECTIVE: To verify the clinical efficacy of Zhang's Xibi formula (ZSXBF) and explain the mechanism underlying its therapeutic effect. METHODS: Preliminary elucidation of the clinical efficacy of ZSXBF in treating KOA in self-control studies, exploration of its mechanism of action with network pharmacology methods, and validation in animal experiments. RESULTS: In clinical studies, ZSXBF administration effectively improved patient quality of life and reduce pain. Network pharmacology was used to explore the possible mechanisms underlying its treatment effect, and after verification in clinical experience and animal experiments, it was found that ZSXBF regulated the expression of immune-related proteins such as IL-17, ERK1, and TP53 in mouse knee joints. CONCLUSION: ZSXBF, which is a traditional Chinese medicine compound that is used to clear heat and detoxify, can effectively improve the clinical symptoms of KOA patients, and its underlying mechanism includes the regulation of human immune-related proteins.

Traditional Chinese medicine external treatment combined with sodium vitrate injection for the treatment of knee osteoarthritis: A meta-analysis.

BACKGROUND: Osteoarthritis of the knee is a clinically common degenerative joint disease that has a high prevalence and, if left untreated, can seriously affect a patient's quality of life. The objective of this article is to systematically evaluate the efficacy and safety of the combination of traditional Chinese medicine external treatment with sodium vitrate injection in the treatment of osteoarthritis of the knee. METHODS: By searching China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database (WF), Chinese Biomedical Literature Database (CBM), Embase, Pubmed, Cochrane Library. The search time was set from 2010 to March 2023. Revman 5.4 software was used for data analysis. The protocol was registered in the PROSPERO database (ref. CRD42023426707). RESULTS: A total of 3239 patients from 31 RCTs were finally included. Meta-analysis showed significant differences in the Total clinical Efficiency (mean difference (MD) = 4.62, 95% Confidence Interval (CI) = 3.52-6.08, P < .01), WOMAC score (MD = 6.57, 95% CI = 5.78-7.36, P < .01), VAS score (MD = 0.26, 95% CI = 0.14-0.37, P < .0001), Lysholm scores (MD = 5.21, 95% CI = 4.51-5.90, P < .0001), and Lequesne index (MD = 5.21, 95% CI = 4.51-5.90, P < .0001) between the Traditional Chinese Medicine External Treatment combined with sodium vitrate injection group and control group. CONCLUSION: The efficacy of traditional Chinese external treatment combined with sodium vitrate injection for osteoarthritis of the knee was superior to that of sodium vitrate injection only in all cases. Due to the limitations of the quantity and quality of the included literature, more high-quality literature is needed to validate this conclusion at a later stage.

[Functionality/isokinetic work of quadriceps in patients with gonarthrosis managed with prolotherapy]. / Funcionalidad/trabajo isocinético de cuádriceps de pacientes con gonartrosis manejados con proloterapia.

Background: Prolotherapy may be a good option in the complementary treatment of knee osteoarthritis (OA) patients, specifically for the increase of functionality. Objective: To determine the effectiveness of prolotherapy in OA grade II - III in the functionality and muscular work of knee flexors and extensors. Material and methods: a double-blind randomized controlled clinical trial was conducted. It included patients diagnosed with OA grades II-III. The experimental group was infiltrated in both knees with 6 ml of 25% glucose solution and 0.05% lidocaine; control group with 0.45% saline solution and 0.05% lidocaine. All patients received a comprehensive rehabilitation program. The isokinetic work of the knee flexor and extensor muscles, pain and functionality were measured, prior to infiltration and at 3-month follow-up. To compare the difference in means, the Student's T test was applied, considering P<0.05 as significant. The project was approved by the local ethics and research committee. Results: 37 patients were recruited, 17 in the prolotherapy group. There were no intergroup differences in functionality, isokinetic knee flexor/extensor work, and pain at baseline, or during follow-up up to 12 weeks. Conclusions: In the present study we identify that both prolotherapy and saline infiltration increased functionality, strength, and decreased pain; however, no statistically significant difference was found between the two group.

Introducción: la proloterapia puede ser buena opción en el tratamiento complementario de pacientes con osteoartrosis de rodilla (OA), específicamente para el incremento de la funcionalidad. Objetivo: determinar la efectividad de la proloterapia en OA grado II-III en la funcionalidad y en el trabajo muscular de flexores y extensores de rodilla. Material y métodos: se realizó un ensayo clínico controlado aleatorizado a doble ciego. Incluyó a pacientes con el diagnostico de OA grados II-III. Al grupo experimental se les infiltraron 6 mL de solución glucosada al 25% y lidocaína al 0.05% en ambas rodillas; al grupo control con solución salina al 0.45% y lidocaína al 0.05%. Todos los pacientes recibieron un programa integral de rehabilitación. Se midió el trabajo isocinético de los músculos flexores y extensores de rodilla, dolor y funcionalidad, previa infiltración y a los tres meses de seguimiento. Para comparar la diferencia de medias, se aplicó la prueba de t de Student, considerando p < 0.05 como significativo. El proyecto se aprobó en el comité local de ética e investigación. Resultados: se reclutaron 37 pacientes, 17 en el grupo de proloterapia. No hubo diferencias intergrupo en la funcionalidad, trabajo isocinético de flexores/extensores de rodilla y dolor iniciales, ni durante el seguimiento hasta las 12 semanas. Conclusiones: en el presente estudio identificó que tanto la proloterapia como la infiltración con solución salina incrementaron la funcionalidad, fuerza y disminuyeron el dolor; sin embargo, no se encontró diferencia estadísticamente significativa entre los dos grupos.

Acute, subchronic toxicity and genotoxicity studies of JointAlive, a traditional Chinese medicine formulation for knee osteoarthritis.

AIM: In vivo and in vitro toxicity tests of JointAlive® were studied in animal models to support the safe use of JointAlive® as a drug for knee osteoarthritis treatment. METHODS: The acute toxicity study in Sprague Dawley (SD) rats was conducted at a 20 g/kg bw/day dose of JointAlive®. For 13-week subchronic toxicity tests, SD rats were orally dosed daily with 0.5, 1.5 and 5 g/kg bw/day of JointAlive®. To assess the potential genotoxicity, Ames test, cellular chromosome aberration and mouse micronucleus test in vivo were carried out. RESULTS: Based on a lack of notable findings other than histopathology finding of co-incidental prostate inflammation at the high dose, the "No Observed Adverse Effect Level (NOAEL)" of JointAlive® was concluded as 5 g/kg bw/day in males and females. Results also indicated that JointAlive® has no risk of genotoxicity. CONCLUSIONS: General toxicity and genotoxicity studies empirically demonstrated that JointAlive® poses a low risk of potential health risks, providing safety supports for the application of JointAlive® as a potential drug candidate to treat knee osteoarthritis.

Potential of thermoresponsive hydrogel as an alternative therapy for rat knee osteoarthritis.

Osteoarthritis is a degenerative condition that is highly prevalent and primarily affects the joints. The knee is the most commonly affected site, impacting the lives of over 300 million individuals worldwide. This study presents a potential solution to address the unmet need for a minimally invasive technique in the treatment of osteoarthritis: a biocompatible, injectable, and thermoresponsive hydrogel. In comparison to commercially available products such as lyophilized platelets, dextrose, and triamcinolone, the thermoresponsive hydrogel exhibits significantly superior performance in dynamic behaviors, including print area, stability, and step cycle, when tested on rats with knee osteoarthritis. However, it demonstrates similar treatment efficacy to these products in static behaviors, as observed through histopathological and immunohistochemical analysis. Therefore, the thermoresponsive hydrogel holds promise as an effective alternative therapy for osteoarthritis. Moreover, by blending the hydrogel with drugs, controlled and sustained release can be achieved, thereby facilitating the long-term management of osteoarthritis symptoms.

Network meta-analysis of 7 acupuncture therapies for knee osteoarthritis.

OBJECTIVE: With the progression of society aging demographic, the prevalence of knee osteoarthritis (KOA) continues to rise steadily, exerting a significant impact on individuals' quality of life. Acupuncture therapy has garnered extensive utilization in the management of osteoarthritis; however, a comprehensive systematic review integrating acupuncture with traditional Chinese medicine remains absent. This study compared the clinical efficacy of 7 acupuncture methods (electroacupuncture, conventional acupuncture, warm needle, floating needle, fire needle, needle knife, and silver needle) for the treatment of KOA through a network meta-analysis. METHODS: This study examined the databases-PubMed, EMbase, The Cochrane Library, the China Biology Medicine, Chinese Journal Full-text Database, Wanfang Database, and VIP Database-for randomized controlled trials of the 7 methods for KOA treatment. The search time spanned from the database establishment to March 5, 2022. The primary outcome indicator was the total effective rate, and the secondary outcome indicator was the visual analog scale. After the layer-by-layer screening, the quality of the literature was assessed using the Cochrane systematic reviewer manual 5.1.0 bias risk assessment tool for randomized controlled trials. After data extraction, the R4.0.1 software was used for network meta-analysis. RESULTS: Based on the network meta-analysis, the ranking of interventions based on the surface under the cumulative ranking curve for the total effective rate is as follows: silver needle (0.99) > floating needle (0.97) > needle knife (0.66) > fire needle (0.56) > warm needle (0.44) > conventional acupuncture (0.35) > electroacupuncture (0.13). Regarding the improvement in visual analog scale scores, the surface under the cumulative ranking curve ranking is as follows: silver needle (0.97) > conventional acupuncture (0.67) > needle knife (0.64) > floating needle (0.51) > warm needle (0.44) > fire needle (0.14) > electroacupuncture (0.09). CONCLUSION: Based on the network meta-analysis, silver needle therapy emerged as the most efficacious and analgesic intervention for KOA. Nevertheless, given the notable variations in the quality and quantity of studies encompassing diverse treatment modalities, the findings of this research necessitate further substantiation through forthcoming high-quality multicenter, large-sample, randomized double-blind trials.