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This study discusses the composition and structure determination of a new multicomponent system from antiinflammatory natural ingredients, consisting of piperine (Pip) and 4-hydroxybenzoic acid (HBA), named Pip-HBA. In addition, this research studied its solubility and anti-inflammatory activity. After screening the stoichiometric proportions, this multicomponent system formation reaction was carried out using the solvent-dropped grinding and evaporation methods. Characterizations using solid analysis including differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and Fourier transform infrared spectroscopy (FTIR), confirmed the formation of Pip-HBA. These multicomponent systems showed different thermograms and diffractograms. Furthermore, the FTIR spectrum of Pip-HBA multicomponent system differs from the physical mixture and its constituent components. Single crystal diffractometry (SCXRD) determined Pip-HBA to be a new multicomponent system structure in three dimensions. Pip-HBA showed increased solubility and anti-inflammatory activity compared to single piperine. Therefore, Pip-HBA multicomponent system has quite potential for further preparation development.

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Osteoarthritis (OA) is a degenerative joint disease primarily affecting the cartilage. The therapeutic potential of the Dipsacus asper-Achyranthes bidentate herb pair for OA has been acknowledged, yet its precise mechanism remains elusive. In this study, we conducted a comprehensive analysis of metabolomic changes and therapeutic outcomes in osteoarthritic rats, employing a gas chromatography-mass spectrometry-based metabolomics approach in conjunction with histopathological and biochemical assessments. The rats were divided into six groups: control, model, positive control, Dipsacus asper treated, Achyranthes bidentata treated, and herb pair treated groups. Compared to the model group, significant reductions in levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and iNOS were observed in the treated groups. Multivariate statistical analyses were employed to investigate metabolite profile changes in serum samples and identify potential biomarkers, revealing 45 differential biomarkers, with eighteen validated using standard substances. These analytes exhibited excellent linearity across a wide concentration range (R2>0.9990), with intra- and inter-day precision RSD values below 4.69% and 4.83%, respectively. Recoveries of the eighteen analytes ranged from 93.97% to 106.59%, with RSD values under 5.72%, underscoring the method's reliability. Treatment with the herbal pair effectively restored levels of unsaturated fatty acids such as linoleic acid and arachidonic acid, along with glucogenic amino acids. Additionally, levels of phosphoric acid and citric acid were reversed, indicating restoration of energy metabolism. Collectively, these findings highlight the utility of metabolomic analysis in evaluating therapeutic efficacy and elucidating the underlying molecular mechanisms of herb pairs in OA treatment.

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During the COVID-19 (coronavirus disease 2019) outbreak, many people were infected, and the symptoms may persist for several weeks or months for recovering patients. This is also known as "long COVID" and includes symptoms such as fatigue, joint pain, muscle pain, et cetera. The COVID-19 virus may trigger hyper-inflammation associated with cytokine levels in the body. COVID-19 can trigger inflammation in the joints, which can lead to osteoarthritis (OA), while long-term COVID-19 symptoms may lead to joint damage and other inflammation problems. According to several studies, sesame has potent anti-inflammatory properties due to its major constituent, sesamin. This study examined sesamin's anti-inflammatory, anti-osteoarthritis, and anti-COVID-19 effects. Moreover, in vivo and in vitro assays were used to determine sesamin's anti-inflammatory activity against the RAW264.7 and SW1353 cell lines. Sesamin had a dose-dependent effect (20 mg/kg) in a monoiodoacetic acid (MIA)-induced osteoarthritis rat model. Sesamin reduced paw swelling and joint discomfort. In addition, the findings indicated that sesamin suppressed the expression of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in the RAW264.7 cell line within the concentration range of 6.25-50 µM. Furthermore, sesamin also had a suppressive effect on MMP (matrix metalloproteinase) expression in chondrocytes and the SW1353 cell line within the same concentration range of 6.25-50 µM. To examine the anti-viral activity, an in silico analysis was performed to evaluate sesamin's binding affinity with SARS-CoV-2 RdRp (severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase) and human ACE2 (angiotensin-converting enzyme 2). Compared to the controls, sesamin exhibited strong binding affinities towards SARS-CoV-2 RdRp and human ACE2. Furthermore, sesamin had a higher binding affinity for the ACE2 target protein. This study suggests that sesamin shows potential anti-SARS-CoV-2 activity for drug development.

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The Zhuanggu Guanjie herbal formula has been a famous Chinese prescription for treating bone diseases since time immemorial. The anti-osteoarthritis (OA) properties of this botanical prescription are well documented in the Chinese Pharmacopoeia. However, the detailed mechanisms behind the phenomenon have not been elucidated. Hence, we aimed to investigate the anti-OA efficacy of the Zhuanggu Guanjie herbal formula and its underlying mechanism. The anti-OA properties of Zhuanggu Guanjie capsule (ZGC) were determined by the cytokine contents and inflammatory-related proteins, which were measured by RT-PCR, flow cytometry, Western blot, and laser confocal assay in ATDC5 cells. The levels of interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin synthesis E2 have been markedly reduced after being treated with ZGC for 48 h in a dose-dependent manner. Furthermore, ZGC prevented the translocation of NF-κB from the cytosol to the nucleus. On the other hand, we used the mono-iodoacetate (MIA)-induced OA model to confirm the in vivo efficacies of this herbal formula. Oral administration of ZGC attenuated MIA-induced OA damage through changes in histopathological and knee joint volumes. The serum matrix metalloproteinase-13 contents in the ZGC treatment group declined as compared to those in the MIA model group. Through our in vitro and in vivo studies, we confirmed the anti-OA efficacy of ZGC and uncovered its detailed mechanism, and this treatment shed light on OA pathophysiology.

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Osteoarthritis (OA) is a chronic inflammatory disorder of the joints caused by fluid and cartilage matrix component reduction. This disease results in symptoms of pain, deformity, and limitation of movement. In general, OA is treated with anti-inflammatory drugs and chondroprotection compounds, includes natural nutraceutical ingredients, which are expected to be effective and have minimal side effects. Arecaceae plants are widely spread worldwide, especially in tropical areas. The objective of this review is to collect information about the Arecaceae family as anti-OA agents, with the main study focusing on the primary and secondary metabolites of plants of the Arecaceae family, i.e., sugar palm (Arenga pinnata), nipa palm (Nypa fruticans), palmyra palm (Borassus flabellifer), date palm (Phoenix dactylifera), and betel nut (Areca catechu) have potential as anti-OA agents. The Arecaceae's metabolites that show anti-inflammatory and chondroprotective effects are galactomannan, fatty acids (linoleic and linolenic acids), flavonoids (quercetin, luteolin, isorhamnetin), phenolics (coumaric acid, ferulic acid), polyphenols (epicatechin), and steroids (stigmasterol, campesterol, spirostane). Based on the reports, the Arecaceae family plants become worthy of being explored and developed into natural anti-OA products, such as supplements or nutraceuticals.

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Punica granatum (P. granatum) is a fruit-bearing tree from the Punicaceae family, indigenous to Iran. This plant has healing qualities that have drawn the interest of the medical community as an alternative treatment for malignancies and non-malignancies. Its healing quality is due to the phytochemicals present in the plant. These include ellagic acid, punicic acid, phenols, and flavonoids. In traditional medicine, P. granatum has been used in treating diseases such as dysentery, bleeding disorders, leprosy, and burns. This review explores the effects of the phytochemical constituents of P. granatum on photodynamic therapy for cancer, chronic inflammation, osteoarthritis, and viral infections. Its antioxidant and antitumor effects play a role in reduced free radical damage and cancer cell proliferation. It was concluded that P. granatum has been used for many disease conditions for a better therapeutic outcome. This paper will give visibility to more studies and expand the knowledge on the potential use of P. granatum in photodynamic cancer treatment.

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The effectiveness of Diacerein as an anti-osteoarthritis drug is limited due to its acutely poor aqueous solubility and bioavailability. The present study demonstrates cocrystallization as a successful technique to improve the biopharmaceutical parameters of diacerein. Three cocrystals of diacerein were prepared by an eco-friendly technique with three suitable coformers namely isonicotinamide, nicotinamide, and theophylline. The formation of a new solid phase was inferred from the DSC thermograms and powder diffraction pattern and was supported by FTIR. The crystal structures of the cocrystals determined from the PXRD pattern using Material Studio software. Detailed analysis showed the formation of supramolecular hetero-synthons of complementary functional groups of the coformers with the carbonyl and carboxyl groups of diacerein. The structural conformation of the cocrystalline state was also provided by the shifts in the ssNMR pattern of the cocrystals. The three new cocrystals were found to have a relatively high solubility and intrinsic dissolution rate which showed remarkable improvement in anti-arthritic activity as compared to diacerein. Thus, proving cocrystallization to be a potential solution to the solubility limited bioavailability problems of diacerein.

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Membrane-free stem cell components (MFSCC) from basal adipose tissue-derived stem cells (ADSCs) are unknown for the treatment strategies in osteoarthritis (OA). OA has been considered to be associated with inflammatory damage and cartilage degradation. In this study, we intended to investigate the molecular mechanism of the anti-inflammation and cartilage protection effect of MFSCC in vitro (rat primary chondrocytes) and in vivo (rat OA model). The MFSCC treatment significantly inhibited interleukin-1α (IL-1α) stimulated inflammation and cartilage degradation. The MFSCC considerably reduced the levels of inflammatory factors such as iNOS, COX-2, NO, and PGE2 and was suppressed NF-κB and MAPKs signaling pathways in IL-1α-stimulated rat chondrocytes. Additionally, biomarkers of OA such as MMP-9, COMP, and CTX-II decreased in the monosodium iodoacetate (MIA)-induced rat OA model by MFSCC treatment. In conclusion, the MFSCC was established to suppress IL-1α induced inflammation and cartilage degradation in vitro and in vivo. These findings provide new insight for understanding OA therapy using membrane-free stem cell approaches.

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In this study, the anti-osteoarthritis effects of Cynanchum wilfordii, Phlomis umbrosa, and Angelica gigas extract (CPAE), observed and confirmed in previously clinical studies were further investigated by in vitro and in vivo studies. Anabolic biomarkers related to healthy cartilage maintenance, such as aggrecan, type II collagen α-1 (Col2a1), sex determining region Y-box-9 (Sox-9), and catabolic biomarkers related to osteoarthritis, such as cyclooxygenase-2 (Cox-2), matrix metalloproteinase-13 (Mmp13), and nuclear factor kappa-light-chain-enhancer of activated B cells (Nfκb), were evaluated by quantitative reverse transcriptase polymerase chain reaction and reporter gene assay. In vitro study results showed significant changes in both anabolic and catabolic biomarkers. For anabolic factors, significant changes in the level of aggrecan (P<0.05), Col2a1 (P<0.05), and Sox-9 (P<0.01) activation were shown after treatment of cartilage cells with CPAE (50 ng/mL) with similar efficacy compared to insulin growth factor, the positive control (100 ng/mL). For catabolic factors, significant changes in the inhibition activity of Cox-2 (P<0.05), Mmp13 (P<0.01), and Nfκb (P<0.05) were shown for CPAE (50 ng/mL) with similar efficacy compared to Celecoxib, the positive control (10 µM). In the in vivo carrageenan-induced paw edema model study results showed that CPAE-treated groups (100 mg/kg) and Celecoxib-treated groups (60 mg/kg) showed comparably significant efficacy of inhibition by 37.1% and 52.1%, respectively. Furthermore, CPAE (200 mg/kg) showed similar effect to Celecoxib (60 mg/kg) with an inhibition rate of 54.3%. This result confirms that CPAE effectively inhibited the inflammation-induced osteoarthritis symptoms.

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OBJECTIVE: Boswellic acid is a plant-derived molecule with putative anti-inflammatory effects. This study was performed to determine whether oral or topical administration of boswellic acid can attenuate joint damage in a mouse model of osteoarthritis (OA). METHODS: Levels of boswellic acid were measured in the blood and synovium of mice treated with oral or topical boswellic acid. OA was generated by surgical destabilization of the medial meniscus (DMM). Therapy with oral or topical boswellic acid was initiated one day after surgery and continued for 12 weeks, when knees were harvested and scored histologically for degree of cartilage loss, osteophyte formation, and synovitis. Microdissected OA synovium was stimulated with IL-1ß or lipopolysaccharide (LPS) in the presence or absence of boswellic acid and cytokine production by quantitative polymerase chain reaction (PCR) or multiplex enzyme linked immunoabsorbant assay (ELISA). RESULTS: Topical treatment resulted in synovial concentrations of boswellic acid 2-6-fold higher than that measured in plasma. Cartilage loss was significantly reduced in mice treated with oral or topical boswellic acid compared with vehicle control (P < 0.01 for both oral and topical therapies). Likewise, treatment with either oral boswellic acid or boswellic acid ointment reduced of synovitis (P = 0.006 and 0.025, respectively) and osteophyte formation (P = 0.009 and 0.030, respectively). In vitro, boswellic acid was able to inhibit IL-1ß and TLR4 mediated induction of several inflammatory mediators from OA synovial explant tissue. CONCLUSIONS: Significant synovial concentration and therapeutic efficacy can be achieved with topical boswellic acid treatment. These findings suggest that boswellic acid has potential as a disease-modifying agent in OA.

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