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Polygonum aviculare L. (PAL), commonly known as knotgrass, has been utilized as a traditional folk medicine across Asian, African, Latin American and Middle Eastern countries to treat various inflammatory diseases, including arthritis and airway inflammation. Numerous medicinal herbs exert anti-inflammatory and antioxidative effects that are mediated through the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of nuclear factor kappa B (NF-κB). However, the underlying molecular mechanisms linking the antioxidative and anti-inflammatory effects remain poorly understood. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that catalyzes heme degradation, ultimately leading to the production of carbon monoxide (CO). Elevated levels of CO have been correlated with the decreased level of inducible nitric oxide synthase (iNOS). In this study, we examined whether HO-1 plays a key role in the relationship between the antioxidative and anti-inflammatory properties of PAL. The anti-inflammatory and antioxidative activities of PAL in an in vitro system were evaluated by determining NF-κB activity, antioxidant response element (ARE) activity, pro-inflammatory cytokine and protein levels, as well as antioxidant protein levels. To examine whether HO-1 inhibition interfered with the anti-inflammatory effect of PAL, we measured nitrite, reactive oxygen species, iNOS, and HO-1 levels in RAW 264.7 murine macrophages pre-treated with Tin protoporphyrin (SnPP, an HO-1 inhibitor). Our results demonstrated that PAL increased ARE activity and the Nrf2-regulated HO-1 level, exerting antioxidative activities in RAW 264.7 macrophages. Additionally, PAL reduced cyclooxygenase-2 (COX-2) and iNOS protein levels by inactivating NF-κB in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Further investigation using the HO-1 inhibitor revealed that HO-1 inhibition promoted iNOS expression, subsequently elevating nitric oxide (NO) generation in LPS-activated RAW 264.7 macrophages treated with PAL compared to those in the macrophages without the HO-1 inhibitor. Overall, our findings suggest that HO-1 induction by PAL may exert anti-inflammatory effects through the reduction of the iNOS protein level. Hence, this study paves the way for further investigation to understand molecular mechanisms underlying the antioxidative and anti-inflammatory activities of medicinal herbs.

The prevalence of ulcerative colitis (UC) has surged in Asian nations recently. The limitations of traditional drug treatments, including biologics, have spurred interest in herbal medicines for managing UC. This study aimed to elucidate the protective mechanisms of hydroethanolic extract from Lepidium apetalum Willdenow (LWE) on intestinal integrity and inflammation in a dextran sodium sulfate (DSS)-induced colitis model of inflammatory bowel disease (IBD). Using UPLC-MS/MS analysis, eleven phytochemicals were identified in LWE, including catechin, vicenin-2, and quercetin. LWE restored transepithelial electrical resistance (TEER) and reduced paracellular permeability in IL-6-stimulated Caco-2 cells, increasing the expression of the tight junction proteins ZO-1 and occludin. LWE treatment alleviated DSS-induced colitis symptoms in mice, reducing body weight loss, disease activity index values, and spleen size, while improving colon length and reducing serum FITC-dextran levels, indicating enhanced intestinal barrier function. LWE suppressed NLRP3 inflammasome activation, reducing protein levels of pro-caspase-1, cleaved-caspase-1, ASC, and NLRP3, as well as mRNA levels of IL-1β, IL-6, and TNF-α. LWE treatment upregulated activity and mRNA levels of the antioxidant enzymes SOD1 and NQO1. Additionally, LWE modulated the Nrf2/Keap1 pathway, increasing p-Nrf2 levels and decreasing Keap1 levels. LWE also restored goblet cell numbers and reduced fibrosis in DSS-induced chronic colitis mice, increasing gene and protein expressions of ZO-1 and occludin. In summary, LWE shows promise as a therapeutic intervention for reducing tissue damage and inflammation by enhancing intestinal barrier function and inhibiting colonic oxidative stress-induced inflammasome activation.

Natural and synthetic chalcones exhibit anti-inflammatory, antitumoral, antibacterial, antifungal, antimalarial, and antitubercular activities. Isodorsmanin A (IDA), a chalcone, is a well-known constituent of the dried seeds of Psoralea corylifolia L. (PC). Although other constituents of PC have been widely investigated, there are no studies on the biological properties of IDA. In this study, we focused on the anti-inflammatory effects of IDA and evaluated its effects on lipopolysaccharide (LPS)-stimulated macrophages. The results showed that IDA suppressed the production of inflammatory mediators (nitric oxide [NO] and prostaglandin E2 [PGE2]) and proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1β [IL-1β]) without cytotoxicity. In addition, it downregulated the mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) within the treatment concentrations. In our mechanistic studies, IDA inhibited the phosphorylation of the c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), and protected the nuclear factor of the kappa light polypeptide gene enhancer in the B-cells’ inhibitor, alpha (IκB-α), from degradation, thus preventing the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells’ (NF-κB) transcription factor. Our results suggest that IDA is a promising compound for attenuating excessive inflammatory responses.

Sinomenium acutum (SA) has long been used as a traditional medicine in China, Japan, and Korea to treat a wide range of diseases. It has been traditionally used to ameliorate inflammation and improve blood circulation. However, its role in platelet activation has not been thoroughly investigated. Hence, we conducted this study to assess the potential inhibitory effect of SA on platelet aggregation and thrombus formation. The antiplatelet activities of SA were evaluated by assessing platelet aggregation, granular secretion, intracellular Ca2+ mobilization, and the Glycoprotein (GP) VI-mediated signalosome. The thrombosis and bleeding time assays were used to investigate the effect of SA (orally administered at 50 and 100 mg/kg for seven days) in mice. SA treatment at concentrations of 50, 100, and 200 μg/mL significantly reduced GPVI-mediated platelet aggregation, granular secretion, and intracellular Ca2+ mobilization. Further biochemical studies revealed that SA inhibited spleen tyrosine kinase, phospholipase Cγ2, phosphatidylinositol 3-kinase, and AKT phosphorylation. Interestingly, oral administration of SA efficiently ameliorated FeCl3-induced arterial thrombus formation without prolonging the tail bleeding time. These findings suggest that SA has beneficial effects in thrombosis and hemostasis. Therefore, SA holds promise as an effective therapeutic agent for the treatment of thrombotic diseases.

The rhizome of Drynaria fortunei (Kunze ex Mett.) J. Sm., which is known as “Golsebo” in Korea, traditionally has been used to heal various inflammatory conditions, including bone metabolism disorders. It relieves blood extravasation, stops bleeding, repairs broken bone tissue, treats bone fractures, and kills bacteria. In this study, we evaluated the modulatory effects of DFP on the differentiation of bone-marrow-derived macrophages into osteoclasts. We performed tartrate-resistant acid phosphatase assays using DFP (at different concentrations and molecular weights) to evaluate the degree of bone resorption in the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis of bone-marrow-derived macrophages. TRAP activity increased with increasing DFP concentrations (0–200 µg/mL). Additionally, DFP significantly inhibited RANKL-induced osteoclastogenesis and controlled RANKL-mediated overexpression of c-Fos and nuclear factor of activated T cells 1, thereby downregulating osteoclast-specific gene (Atp6v0d2, cathepsin K, and DC-STAMP) expression. DFP thus has potential as a nutraceutical candidate for treating bone loss diseases, including osteoporosis in postmenopausal women.

In this study, a method to both qualitatively and quantitively analyze the components of Oryeong-san (ORS), which is composed of five herbal medicines (Alisma orientale Juzepzuk, Polyporus umbellatus Fries, Atractylodes japonica Koidzumi, Poria cocos Wolf, and Cinnamomum cassia Presl) and is prescribed in traditional Oriental medicine practices, was established for the first time. First, ORS components were profiled using ultra-high-performance liquid chromatography/quadrupole Orbitrap mass spectrometry, and 19 compounds were clearly identified via comparison against reference standard compounds. Subsequently, a quantitative method based on ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry was established to simultaneously measure the identified compounds. Nineteen compounds were accurately quantified using the multiple-reaction-monitoring mode and used to analyze the sample; we confirmed that coumarin was the most abundant compound. The method was validated, achieving good linearity (R2 ≤ 0.9991), recovery (RSD, 0.11–3.15%), and precision (RSD, 0.35–9.44%). The results suggest that this method offers a strategy for accurately and effectively determining the components of ORS, and it can be used for quality assessment and management.

Allergic rhinitis (AR) is a common upper-airway inflammatory disease of the nasal mucosa caused by immunoglobulin (IgE)-mediated inflammation. AR causes various painful clinical symptoms of the nasal mucosa that worsen the quality of daily life, necessitating the urgent development of therapeutic agents. Herein, we investigated the effects of Caesalpinia sappan Linn. heartwood water extract (CSLW), which has anti-inflammatory and antioxidant properties, on AR-related inflammatory responses. We examined the anti-inflammatory and anti-allergic effects of CSLW in ovalbumin (OVA)-induced AR mice and in primary human nasal epithelial cells (HNEpCs). Administration of CSLW mitigated allergic nasal symptoms in AR mice, decreased total immune cell and eosinophil counts in nasal lavage fluid, and significantly reduced serum levels of OVA-specific IgE, histamine, and Th2 inflammation-related cytokines. CSLW also inhibited the infiltration of several inflammatory and goblet cells, thereby ameliorating OVA-induced thickening of the nasal mucosa tissue. We found that CSLW treatment significantly reduced infiltration of eosinophils and production of periostin, MUC5AC, and intracellular reactive oxygen species through the Keap1/Nrf2/HO-1 pathway in HNEpCs. Thus, our findings strongly indicate that CSLW is a potent therapeutic agent for AR and can improve the daily life of patients by controlling the allergic inflammatory reaction of the nasal epithelium.

Jinmu-tang (JMT) is a traditional herbal medicine consisting of five herbal medicines: Poria cocos Wolf, Paeonia lactiflora Pallas, Zingiber officinale Roscoe, Atractylodes japonica Koidzumi, and Aconitum carmichaeli Debeaux. In this study, the JMT components were profiled using UHPLC-Q-Orbitrap-MS, and 23 compounds were identified and characterized. In addition, UPLC-TQ-MS/MS analysis was performed in the positive and negative ion modes of an electrospray ionization source for the simultaneous quantification of the identified compounds. The multiple reaction monitoring (MRM) method was established to increase the sensitivity of the quantitative analysis, and the method was verified through linearity, recovery, and precision. All analytes showed good linearity (R2 ≤ 0.9990). Moreover, the recovery and the relative standard deviation of precision were 86.19–114.62% and 0.20–8.00%, respectively. Using the established MRM analysis method, paeoniflorin was found to be the most abundant compound in JMT. In conclusion, these results provide information on the constituents of JMT and can be applied to quality control and evaluation.

In traditional oriental medicines, Commiphora myrrha and its resinous exudate (i.e., myrrh) are used as herbal remedies to treat various inflammatory and metabolic disorders. Until now, C. myrrha-derived herbal products are considered useful source for bioactive compounds to manage numerous human diseases. This study investigated the effects of water extract of C. myrrha resin (WCM) and its polysaccharide (WCM-PE) on modulatory effects of osteoclast differentiation and/or ovariectomized-induced bone loss. Oral administration of WCM (200 and 500 mg/kg/day for four weeks) notably decreased trabecular bone loss and lipid accumulation in the bone marrow cavity. WCM and WCM-PE dose-dependently inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and suppressed RANKL-mediated overexpression of c-Fos and nuclear factor of activated T cells, cytoplasmic 1, thereby downregulating osteoclast-specific gene (Atp6v0d2, DC-STAMP and cathepsin K) expression. Thus, our results suggest that WCM and WCM-PE are promising nutraceutical candidates for the management of osteoporosis in postmenopausal women.

In traditional oriental medicine, Drynaria roosii Nakaike is widely used in treating bone diseases. Postmenopausal women are strongly associated with osteoporosis and obesity. This study aimed to investigate the effects of the water extract of D. roosii (WDR) on bone loss and obesity in ovariectomized (OVX) mice fed a high-fat diet (HFD). Body weight, gonadal fat weight, histological findings, and morphometric parameters in trabecular bone were evaluated after OVX mice were treated with WDR and HFD for four weeks. The receptor activator of nuclear κ-B ligand (RANKL)-induced osteoclast differentiation in bone marrow-derived macrophages (BMMs) was examined. Phytochemical identification of WDR using ultrahigh-performance liquid chromatography−tandem mass spectrometry was performed. WDR reversed the changes in body weight gain, gonadal fat mass, and trabecular bone parameters by ovariectomy. However, ovariectomy-induced uterine atrophy was not affected by WDR. WDR decreased adipocyte size and pro-inflammatory cytokines (interleukin (IL)-1β and IL-6) in gonadal fats and lipid accumulation in the bone marrow, which were induced by ovariectomy. WDR significantly decreased RANKL-induced osteoclast differentiation in BMMs. Fifteen phytochemicals were identified in WDR: Seven and nine with anti-osteoporotic and anti-adipogenic activities, respectively. Our findings suggest that WDR may have beneficial effects on postmenopausal osteoporosis and obesity.

Purpose: The purpose of this study was to determine the clinical efficacy of low-frequency intravitreal ranibizumab to treat macular edema due to retinal vein occlusion (RVO). Patients and methods: This was a retrospective examination of cases that received intravitreal ranibizumab for untreated RVO over a period of 12 months. Instead of the conventional three monthly injections, injections were given once during the introductory period. If the recurrence of macular edema was diagnosed during the monthly visit, additional injections were given as needed. There were 21 eyes of 21 patients with branch RVO (BRVO) and ten eyes of ten patients with central RVO (CRVO). The parameters examined included the number of injections over the 12-month period, improvements in best-corrected visual acuity (BCVA), and the central macular thickness (CMT). For BRVO, preinjection parameters that had an effect on the prognosis of BCVA after the 12-month period were also examined. Results: The total mean number of injections over the 12-month period was 3.4 for CRVO and 2.1 for BRVO. For CRVO, the BCVA in log minimum angular resolution changed from a preinjection value of 0.80 to 0.55 at 12 months. For BRVO, the change was from 0.51 to 0.30. For all diseases, BCVA improved after 12 months compared with the preinjection values (P,0.05). There was improvement in the CMT, and the CRVO changed from 765.0 µm at preinjection to 253.5 µm 12 months later. BRVO changed from 524.1 to 250.1 µm, and preinjection BCVA was associated with a prognosis of visual acuity after 12 months of the initial injection (P=0.0485). Results: The total mean number of injections over the 12-month period was 3.4 for CRVO and 2.1 for BRVO. For CRVO, the BCVA in log minimum angular resolution changed from a preinjection value of 0.80 to 0.55 at 12 months. For BRVO, the change was from 0.51 to 0.30. For all diseases, BCVA improved after 12 months compared with the preinjection values (P,0.05). There was improvement in the CMT, and the CRVO changed from 765.0 µm at preinjection to 253.5 µm 12 months later. BRVO changed from 524.1 to 250.1 µm, and preinjection BCVA was associated with a prognosis of visual acuity after 12 months of the initial injection (P=0.0485). [ABSTRACT FROM AUTHOR]