Kaempferia parviflora Extract Alleviated Rat Arthritis,Exerted Chondroprotective Properties In Vitro,and Reduced Expression of Genes Associated with Inflammatory Arthritis

Kaempferia parviflora Wall. ex Baker (KP) has been reported to attenuate cartilage destruction in rat model of osteoarthritis. Previously, we demonstrated that KP rhizome extract and its active components effectively suppressed mechanisms associated with RA in SW982 cells. Here, we further evaluated the anti-arthritis potential of KP extract by using multi-level models, including a complete Freund’s adjuvant-induced arthritis and a cartilage explant culture model, and to investigate the effects of KP extract and its major components on related gene expressions and underlying mechanisms within cells. In arthritis rats, the KP extract reduced arthritis indexes, with no significant changes in biological parameters. In the cartilage explant model, the KP extract exerted chondroprotective potential by suppressing sulfated glycosaminoglycans release while preserving high accumulation of proteoglycans. In human chondrocyte cell line, a mixture of the major components equal to their amounts in KP extract showed strong suppression the expression of genes-associated inflammatory joint disease similar to that of the extract. Additionally, KP extract significantly suppressed NF-κB and MAPK signaling pathways. The suppressing expression of necroptosis genes and promoted anti-apoptosis were also found. Collectively, these results provided supportive evidence of the anti-arthritis properties of KP extract, which are associated with its three major components.     

Anti-inflammatory bibenzyls from the stems of Dendrobium huoshanense via bioassay guided isolation

Abstract

The stems of Dendrobium huoshanense have long been used to prevent various diseases, including inflammatory diseases. This study was aimed to explain the anti-inflammatory effect of D. huoshanense stems in LPS-induced RAW 264.7 macrophages and to discover potential anti-inflammatory compounds. Results exhibited that D. huoshanense stems ethanol extract could significantly inhibit LPS-induced production of NO, TNF-α and IL-1β. Based on bioassay guided strategy, four bibenzyls (1–4) were isolated from D. huoshanense stems for the first time. Anti-inflammatory assay showed 1–4 could remarkably inhibit the production of NO in LPS-induced macrophages. Moreover, quantitative RT-PCR analysis displayed that the mRNA levels of iNOs, TNF-α and IL-1β could also be significantly reduced by 1–4. These results suggested that D. huoshanense stems ethanol extract and bibenzyls 1–4 might be well developed as therapeutic agent to prevent inflammatory diseases.     

Health-Promoting Properties of Medicinal Mushrooms and Their Bioactive Compounds for the COVID-19 Era—An Appraisal: Do the Pro-Health Claims Measure Up?

Many mushroom species are consumed as food, while significant numbers are also utilised medicinally. Mushrooms are rich in nutrients and bioactive compounds. A growing body of in vitro, in vivo, and human research has revealed their therapeutic potentials, which include such properties as anti-pathogenic, antioxidant, anti-inflammatory, immunomodulatory, gut microbiota enhancement, and angiotensin-converting enzyme 2 specificity. The uses of medicinal mushrooms (MMs) as extracts in nutraceuticals and other functional food and health products are burgeoning. COVID-19 presents an opportunity to consider how, and if, specific MM compounds might be utilised therapeutically to mitigate associated risk factors, reduce disease severity, and support recovery. As vaccines become a mainstay, MMs may have the potential as an adjunct therapy to enhance immunity. In the context of COVID-19, this review explores current research about MMs to identify the key properties claimed to confer health benefits. Considered also are barriers or limitations that may impact general recommendations on MMs as therapy. It is contended that the extraction method used to isolate bioactive compounds must be a primary consideration for efficacious targeting of physiological endpoints. Mushrooms commonly available for culinary use and obtainable as a dietary supplement for medicinal purposes are included in this review. Specific properties related to these mushrooms have been considered due to their potential protective and mediating effects on human exposure to the SARS CoV-2 virus and the ensuing COVID-19 disease processes.     

An efficient high-speed counter-current chromatography method for the preparative separation of sesquiterpenoids from the rhizomes of Cyperus rotundus L. combined with evaluation of the anti-inflammation activity in vitro and molecular docking

Cyperus rotundus L. has been extensively used in ancient medication for the treatment of different disorders worldwide, in which sesquiterpenes are the most representative components. In this study, sesquiterpenes were effectively purified by two-dimensional counter-current chromatography in combination with continuous injection and inner-recycling mode with a solvent system of n-hexane/ethyl acetate/methanol/water (1:0.2:1:0.2, v/v/v/v). For one-dimension separation, continuous injection mode was used with three times injection and the inner-recycling mode was adopted for the separation of two mixtures for two-dimensional separation. Finally, four sesquiterpenoids, including scariodione ( 1 ), cyperenoic acid ( 2 ), scariodione ( 3 ), and α-cyperone ( 4 ), were obtained with purities over 98%. Mass spectrometry and nuclear magnetic resonance were applied to identify their structures. The results from the anti-inflammation effect with zebrafish demonstrated that cyperenoic acid exhibited stronger anti-inflammation activity. Molecular docking results suggested that cyperenoic acid possessed lower binding energies –9.4545 kcal/mol with 1CX2 to form formed hydrogen bond interaction with ARG120. In general, all the obtained findings proved that the strong anti-inflammation capacity of cyperenoic acid can have the potential of being adopted for treating diseases resulting from inflammation.     

6,8-di-C-glycosyl flavones with β-furanoarabinose from Scutellaria baicalensis and their anti-inflammatory activities

Two flavone di-C-glycosides, a pair of isomers, were isolated from Scutellaria baicalensis. The structures of compounds 1 and 2 were elucidated by means of physical data, including 1D and 2D NMR and HR-ESI-MS. Supporting theoretical calculations of the compound conformational landscape has also been conducted for geometry optimization. This is the first report of the natural occurrence of β-furanoarabinoside. In addition, the effects of compounds 1 and 2 on NO, pro-inflammatory cytokines, PGE2 and COX-2 levels were measured in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. The pair of isomers exhibited significant inhibitory effects on inflammation.     

Diterpenoid Compounds Isolated from Chloranthus oldhamii Solms Exert Anti-Inflammatory Effects by Inhibiting the IKK/NF-κB Pathway

Chloranthus oldhamii Solms (CO) is a folk medicine for treating infection and arthritis pain but its pharmacological activity and bioactive compounds remain mostly uncharacterized. In this study, the anti-inflammatory compounds of C. oldhamii were identified using an LPS-stimulated, NF-κB-responsive RAW 264.7 macrophage reporter line. Three diterpenoid compounds, 3α-hydroxy-ent-abieta-8,11,13-triene (CO-9), 3α, 7β-dihydroxy-ent-abieta-8,11,13-triene (CO-10), and decandrin B (CO-15) were found to inhibit NF-κB activity at nontoxic concentrations. Moreover, CO-9 and CO-10 suppressed the expression of IL-6 and TNF-α in LPS-stimulated RAW 264.7 cells. The inhibitory effect of CO-9 on TNF-α and IL-6 expression was further demonstrated using LPS-treated bone marrow-derived macrophages. Furthermore, CO-9, CO-10, and CO-15 suppressed LPS-triggered COX-2 expression and downstream PGE2 production in RAW 264.7 cells. CO-9 and CO-10 also reduced LPS-triggered iNOS expression and nitrogen oxide production in RAW 264.7 cells. The anti-inflammatory mechanism of the most effective compound, CO-9, was further investigated. CO-9 attenuated LPS-induced NF-κB activation by reducing the phosphorylation of IKKα/β (Ser176/180), IκBα (Ser32), and p65 (Ser534). Conversely, CO-9 did not affect the LPS-induced activation of MAPK signaling pathways. In summary, this study revealed new anti-inflammatory diterpenoid compounds from C. oldhamii and demonstrated that the IKK-mediated NK-κB pathway is the major target of these compounds.     

Characterization,Antioxidant and Anti-Inflammation Capacities of Fermented Flammulina velutipes Polyphenols

This work investigated the preparation, characterization, antioxidant, and anti-inflammation capacities of Flammulina velutipes polyphenols (FVP) and fermented FVP (FFVP). The results revealed that the new syringic acid, accounting for 22.22%, was obtained after fermentation (FFVP). FFVP exhibits higher antioxidant and anti-inflammation activities than FVP, enhancing cell viability and phagocytosis, inhibiting the secretion of NO and ROS, and reducing the inflammatory response of RAW264.7 cells. This study revealed that FFVP provides a theoretical reference for in-depth study of its regulatory mechanisms and further development of functional antioxidants that are applicable in the food and health industry.     

Aurones and Flavonols from Coreopsis lanceolata L. Flowers and Their Anti-Oxidant,Pro-Inflammatory Inhibition Effects,and Recovery Effects on Alloxan-Induced Pancreatic Islets in Zebrafish

(1) Background: Many flavonoids have been reported to exhibit pharmacological activity; a preparatory study confirmed that Coreopsis lanceolata flowers (CLFs) contained high flavonoid structure content; (2) Methods: CLFs were extracted in aqueous methanol (MeOH:H₂O = 4:1) and fractionated into acetic ester (EtOAc), normal butanol (n-BuOH), and H₂O fractions. Repeated column chromatographies for two fractions led to the isolation of two aurones and two flavonols; (3) Results: Four flavonoids were identified based on a variety of spectroscopic data analyses to be leptosidin (1), leptosin (2), isoquercetin (3), and astragalin (4), respectively. This is the first report for isolation of 2–4 from CLFs. High-performance liquid chromatography (HPLC) analysis determined the content levels of compounds 1–4 in the MeOH extract to be 2.8 ± 0.3 mg/g (1), 17.9 ± 0.9 mg/g (2), 3.0 ± 0.2 mg/g (3), and 10.9 ± 0.9 mg/g (4), respectively. All isolated compounds showed radical scavenging activities and recovery activities in Caco-2, RAW264.7, PC-12, and HepG2 cells against reactive oxygen species. MeOH extract, EtOAc fraction, and 1–3 suppressed NO formation in LPS-stimulated RAW 264.7 cells and decreased iNOS and COX-2 expression. Furthermore, all compounds recovered the pancreatic islets damaged by alloxan treatment in zebrafish; (4) Conclusions: The outcome proposes 1–4 to serve as components of CLFs in standardizing anti-oxidant, pro-inflammatory inhibition, and potential anti-diabetic agents.     

Anti-Inflammatory and Antinociceptive Activities of the Essential Oil of Tagetes parryi A. Gray (Asteraceae) and Verbenone

Tagetes parryi is a plant empirically used to treat gastrointestinal and inflammatory diseases, its essential oil (EOTP) was obtained from the aerial parts, and the composition was elucidated by GC-MS. The in vivo and in vitro anti-inflammatory activities and the antinociceptive activity of EOTP and (1S)-(-)-verbenone (VERB) were assessed. The major compounds identified for EOTP were verbenone (33.39%), dihydrotagetone (26.88%), and tagetone (20.8%). EOTP and VERB diminished the ear oedema induced with TPA by 93.77 % and 81.13 %, respectively. EOTP and VERB decreased inflammation in a 12-O-tetradecanoylphorbol-13-acetate (TPA) chronic model with ED₅₀ = 54.95 mg/kg and 45.24 mg/kg, respectively. EOTP (15 µg/mL) inhibited the in vitro production of the pro-inflammatory mediators NO (67.02%), TNF-α (69.21%), and IL-6 (58.44%) in LPS-stimulated macrophages. In the acetic induced writhing test, EOTP and VERB showed antinociceptive effects with ED₅₀ = 84.93 mg/kg and ED₅₀ = 45.24 mg/kg, respectively. In phase 1 of the formalin test, EOTP and VERB showed no antinociceptive effects, whereas in phase 2, EOTP (ED₅₀ = 35.45 mg/kg) and VERB (ED₅₀ = 24.84 mg/kg) showed antinociceptive effects. The antinociceptive actions of ETOP and VERB were blocked with the co-administration of L-NAME. This study suggests that EOTP and VERB might be used in the treatment of pain and inflammatory problems.     

N-Butyrylated Hyaluronic Acid Achieves Anti-Inflammatory Effects In Vitro and in Adjuvant-Induced Immune Activation in Rats

Previously synthesized N-butyrylated hyaluronic acid (BHA) provides anti-inflammatory effects in rat models of acute gouty arthritis and hyperuricemia. However, the mechanism of action remains to be elucidated. Herein, the anti-inflammatory and antioxidative activities of BHA and the targeted signaling pathways were explored with LPS-induced RAW264.7 and an adjuvant-induced inflammation in a rat model. Results indicated that BHA inhibited the generation of pro-inflammatory cytokines TNFα, IL-1β and IL-6, reduced ROS production and down-regulated JAK1-STAT1/3 signaling pathways in LPS-induced RAW264.7. In vivo, BHA alleviated paw and joint swelling, decreased inflammatory cell infiltration in paw tissues, suppressed gene expressions of p38 and p65, down-regulated the NF-κB and MAPK signaling pathways and reduced protein levels of TNFα, IL-1β and IL-6 in joint tissues of arthritis rats. This study demonstrated the pivotal role of BHA in anti-inflammation and anti-oxidation, suggesting the potential clinical value of BHA in the prevention of inflammatory arthritis and is worthy for development as a new pharmacological treatment.