Antrodia cinnamomea prevents ovariectomized-promoted bone loss by inhibiting osteoclast formation.

Osteoporosis is a common bone disease in aging populations, particularly in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are linked with a variety of adverse effects. Antrodia cinnamomea extracts (ACE) are highly renowned for their anticancer, antioxidative, and anti-inflammatory properties. However, whether ACE-enriched anti-osteoporosis functions are largely unknown. In a preclinical animal model, we found that ovariectomy significantly decreased bone volume in the ovariectomized (OVX) rats. Administration of ACE antagonized OVX-induced bone loss. In addition, ACE reversed OVX-reduced biomechanical properties. The serum osteoclast marker also showed improvement in the ACE-treated group. In the cellular model, it was indicated that ACE inhibits RANKL-induced osteoclast formation. Taken together, ACE seems to be a hopeful candidate for the development of novel anti-osteoporosis treatment.

Synthesis of bioactive evodiamine and rutaecarpine analogues under ball milling conditions.

Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC50 of 0.75 ± 0.04 µg mL-1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches.

The Efficacy of Lactobacillus delbrueckii ssp. bulgaricus Supplementation in Managing Body Weight and Blood Lipids of People with Overweight: A Randomized Pilot Trial.

This study aimed to evaluate the efficacy of Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) in improving body weight, obesity-related outcomes, and lipid profiles of overweight people. Thirty-six overweight participants were randomly assigned to either a probiotic or a placebo group. A placebo powder or L. bulgaricus powder (containing 1 × 108 colony-forming unit (CFU) of the probiotic) was administered daily for 12 weeks. Body composition was determined, and blood tests were performed before and after the intervention. L. bulgaricus supplementation under the present condition did not affect the body weight, fat percentage, or body mass index (BMI) of the participants, while it resulted in a notable decrease in blood triglyceride (TG) levels, which corresponded to a lowering of the TG proportion in the composition of large VLDL (L-XXL sized fractions) and HDL (M and L fractions) in the probiotic-treated group. These results suggest that L. bulgaricus supplementation under the current conditions may not be helpful for losing weight, but it has the potential to decrease blood TG levels by modulating TG accumulation in or transport by VLDL/HDL in obese patients. L. bulgaricus supplements may have health-promoting properties in preventing TG-related diseases in overweight people.

Effects of Citrus depressa Hayata juice on high-fat diet-induced obesity in HBV transgenic mice.

The present study investigated the potential anti-obesity properties of Citrus depressa Hayata (CDH) juice in HBV transgenic mice, as well as the impact of fermentation on the effectiveness of the juice. The results revealed that fermentation increased the levels of polyphenols and hesperidin in CDH juice. The animal study demonstrated that both juices were effective in mitigating the weight gain induced by a high-fat diet by correcting metabolic parameter imbalances, reducing hepatic lipid accumulation, and reversing hepatic immune suppression. Furthermore, fermented juice exhibited superior efficacy in managing body weight and inhibiting the expansion of white adipose tissue (WAT). Fermented juice significantly enhanced adiponectin production and PPARγ expression in WAT, while also reducing hypertrophy. This study offers valuable insights into the potential role of CDH juices in combating obesity associated with high fat consumption and underscores the promise of CDH juice as a functional beverage.

Inhibition of ADAM9 promotes the selective degradation of KRAS and sensitizes pancreatic cancers to chemotherapy.

Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PDAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (ADAM)9 as a modulator of PDAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, ADAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS. Suppression of ADAM9 by a small-molecule inhibitor restricts disease progression in spontaneous models, and combination with gemcitabine elicits dramatic regression of patient-derived tumors. Our findings provide a promising strategy to target the KRAS signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in PDAC.

Application of response surface methodology and quantitative NMR for the optimum extraction, characterization, and quantitation of Antrodia cinnamomea triterpenoids.

Antrodia cinnamomea (AC) is a treasured Asian medicinal mushroom, which has attracted attention due to recent research on its effectiveness in targeting a variety of serious ailments such as cancer and liver diseases. Among different A. cinnamomea constituents, triterpenoids are regarded as the most therapeutically attractive components because of their anti-inflammatory and cytotoxic activities. In the present study, we proposed a mathematical and statistical extraction protocol to evaluate the concentrations of total ergostane and lanostane triterpenoid derivatives from the ethanolic extract of the wild fruiting bodies of A. cinnamomea (EEAC) by utilizing response surface methodology (RSM) and quantitative NMR (qNMR) approaches. The optimum response surface model showed that the variations of the investigated response variables reached more than 90%, suggesting that the developed model is accurate in explaining response variability. Furthermore, the EEAC major characteristic triterpenoids were quantified through the comparison of the HPLC-tandem MS results with those of the qNMR results. The precision of the used techniques was also evaluated. The experimental design of the EEAC optimum extraction procedure obtained by using RSM and qNMR enabled accurate characterization and quantitation of A. cinnamomea triterpenoids.

Association of combination antiretroviral therapy with risk of neurological diseases in patients with HIV/AIDS in Taiwan: a nested case-control study.

Heterogeneous neurocognitive impairment remains an important issue, even in the era of combination antiretroviral therapy (cART), with an incidence ranging from 15% to 65%. Although ART drugs with higher penetration scores to the central nervous system (CNS) show better HIV replication control in the CNS, the association between CNS penetration effectiveness (CPE) scores and neurocognitive impairment remains inconclusive. To explore whether ART exposure is associated with the risk of neurological diseases among patients with HIV/AIDS, this study in Taiwan involved 2,571 patients with neurological diseases and 10,284 matched, randomly selected patients without neurological diseases between 2010 and 2017. A conditional logistic regression model was used in this study. The parameters for ART exposure included ART usage, timing of exposure, cumulative defined daily dose (DDD), adherence, and cumulative CPE score. Incident cases of neurological diseases, including CNS infections, cognitive disorders, vasculopathy, and peripheral neuropathy, were obtained from the National Health Insurance Research Database in Taiwan. Odds ratios (ORs) for the risk of neurological diseases were conducted using a multivariate conditional logistic regression model. Patients with a history of past exposure (OR: 1.68, 95% confidence interval [CI]:1.22-2.32), low cumulative DDDs (< 2,500) (OR: 1.28, 95% CI: 1.15-1.42), low adherence (0 < adherence (ADH) ≤ 0.8) (OR: 1.46, 95% CI: 1.30-1.64), or high cumulative CPE scores (>14) (OR: 1.34, 95% CI: 1.14-1.57) had a high risk of neurological diseases. When stratified by classes of ART drugs, patients with low cumulative DDDs or low adherence had a high risk of neurological diseases, including NRTIs, PIs, NNRTIs, INSTIs, and multi-drug tablets. Subgroup analyses also suggested that patients with low cumulative DDDs or low adherence had a high risk of neurological diseases when they had high cumulative CPE scores. Patients with high cumulative DDDs or medication adherence were protected against neurological diseases only when they had low cumulative CPE scores (≤ 14). Patients may be at risk for neurological diseases when they have low cumulative DDDs, low adherence, or usage with high cumulative CPE scores. Continuous usage and low cumulative CPE scores of ART drugs may benefit neurocognitive health in patients with HIV/AIDS.

Umbelliferone and eriodictyol suppress the cellular entry of SARS-CoV-2.

BACKGROUND: Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study. RESULTS: Among the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice. CONCLUSIONS: Eriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2.

High-Purity Bioactive Ingredient-3S,3'S-Astaxanthin: A New Preparation from Genetically Modified Kluyveromyces marxianus without Column Chromatography and Gel Filtration.

A highly efficient methodology for bioactive ingredient 3S,3'S-astaxanthin (3S,3'S-AST) preparation from genetically modified yeast (Kluyveromyces marxianus) with a combination of enzyme-assisted extraction and salt-assisted liquid-liquid extraction (SALLE) was achieved. The highest yield of 3S,3'S-AST indicated that FoodPro® CBL for yeast cell walls hydrolysis could significantly enhance extraction and obtain, with the help of SALLE procedure, quantified 3S,3'S-AST over 99% in purity through cation chelation. In the oxygen radical antioxidant capacity (ORAC) assay, the antioxidant capacity of high-purity 3S,3'S-AST products were 18.3 times higher than that of the original raw material extract. This new combination preparation may replace previous methods and has the potential to be scaled up in the manufacture of high-purity 3S,3'S-AST from low-value bioresources of raw materials to high-value products in the food and/or drug industries with lower cost and simple equipment.

Effect of Chinese herbal medicine therapy on risks of all-cause mortality, infections, parasites, and circulatory-related mortality in HIV/AIDS patients with neurological diseases.

Introduction: Long-term living with human immunodeficiency virus (HIV) and/or antiretroviral therapy (ART) is associated with various adverse effects, including neurocognitive impairment. Heterogeneous neurocognitive impairment remains an important issue, affecting between 15-65% of human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) patients and resulting in work performance, safety, and health-related outcomes that have a heavy economic burden. Methods: We identified 1,209 HIV/AIDS patients with neurological diseases during 2010-2017. The Kaplan-Meier method, log-rank test, and Cox proportional hazards model were used to analyze 308 CHM users and 901 non-CHM users within this population. Major CHM clusters were determined using association rule mining and network analysis. Results and Discussion: Results showed that CHM users had a 70% lower risk of all-cause mortality (adjusted hazard ratio (aHR) = 0.30, 95% confidence interval (CI):0.16-0.58, p < 0.001) (p = 0.0007, log-rank test). Furthermore, CHM users had an 86% lower risk of infections, parasites, and circulatory-related mortality (aHR = 0.14, 95% confidence interval (CI):0.04-0.46, p = 0.001) (p = 0.0010, log-rank test). Association rule mining and network analysis showed that two CHM clusters were important for patients with neurological diseases. In the first CHM cluster, Huang Qin (HQ; root of Scutellaria baicalensis Georgi), Gan Cao (GC; root of Glycyrrhiza uralensis Fisch.), Huang Lian (HL; root of Coptis chinensis Franch.), Jie Geng (JG; root of Platycodon grandiflorus (Jacq.) A.DC.), and Huang Bai (HB; bark of Phellodendron amurense Rupr.) were identified as important CHMs. Among them, the strongest connection strength was identified between the HL and HQ. In the second CHM cluster, Suan-Zao-Ren-Tang (SZRT) and Ye Jiao Teng (YJT; stem of Polygonum multiflorum Thunb.) were identified as important CHMs with the strongest connection strength. CHMs may thus be effective in treating HIV/AIDS patients with neurological diseases, and future clinical trials are essential for the prevention of neurological dysfunction in the population.

The Use of San-Huang-Xie-Xin-Tang Reduces the Mortality Rate among Breast Cancer Patients.

Globally, breast cancer is the most common cause of cancer deaths. In Taiwan, it is the most prevalent cancer among females. Since San-Huang-Xie-Xin-Tang (SHXXT) exerts not only an anti-inflammatory but an immunomodulatory effect, it may act as a potent anti-tumor agent. Herein, the study aimed to explore the influence of SHXXT and its constituents on the mortality rate among breast cancer patients in Taiwan regarding the component effect and the dose-relationship effect. By using the Taiwan National Health Insurance (NHI) Research Database (NHIRD), the study analyzed 5387 breast cancer patients taking Chinese herbal medicine (CHM) and 5387 breast cancer patients not using CHM. CHM means SHXXT and its constituents in the study. The Kaplan-Meier method was utilized to determine the mortality probabilities among patients. Whether the CHM influences the mortality rate among patients was estimated by Cox proportional hazard regression analysis. The use of CHM could lower the cancer mortality rate by 59% in breast cancer patients. The protective effect was parallel to the cumulative days of CHM use and the annual average CHM dose. In addition, the mortality rate was lower in patients who used SHXXT compared to those who only used one of its constituents. SHXXT and its constituents were all promising therapeutic weapons against breast cancer.

Briavioids E-G, Newly Isolated Briarane-Diterpenoids from a Cultured Octocoral Briareum violaceum.

The chemical screening of a cultured soft coral, Briareum violaceum, led to the isolation of eight natural, briarane-related diterpenoids, including three unreported metabolites, briavioids E-G (1-3), and five known briaranes, briacavatolides B (4) and C (5), briaexcavatin L (6), briaexcavatolide U (7) and briarenol K (8). The structures of briaranes 1-8 were established using spectroscopic methods. The absolute configuration of briavioid A (9), obtained in a previous study, was reported for the first time in this study by a single-crystal X-ray diffraction analysis using a copper radiation source. The anti-inflammatory activity of briaranes 1 and 2 and briaranes 4-8 was evaluated by screening their inhibitory ability against the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells.

Development on potential skin anti-aging agents of Cosmos caudatus Kunth via inhibition of collagenase, MMP-1 and MMP-3 activities.

BACKGROUND: Skin aging is associated with degradation of collagen by matrix metalloproteinases (MMPs), which leads to loss of skin elasticity and formation of wrinkles. Cosmos caudatus Kunth (CC) has been traditionally claimed as an anti-aging agent in Malaysia. Despite its well-known antioxidant activity, the anti-aging properties of CC was not validated. PURPOSE: This study aimed to investigate the anti-aging potential of CC extracts and fractions, particularly their inhibition of collagenase, MMP-1 and MMP-3 activities in human dermal fibroblasts CCD-966SK, followed by isolation, identification and analysis of their bioactive constituents. STUDY DESIGN AND METHODS: DPPH assay was firstly used to evaluate the antioxidant activity throughout the bioactivity-guided fractionation. Cell viability was determined using MTS assay. Collagenase activity was examined, while MMP-1 and MMP-3 expression were measured using qRT-PCR and western blotting. Then, chemical identification of pure compounds isolated from CC fractions was done by using ESIMS, 1H and 13C NMR spectroscopies. HPLC analyses were carried out for bioactive fractions to quantify the major components. RESULTS: Throughout the antioxidant activity-guided fractionation, fractions CC-E2 and CC-E3 with antioxidant activity and no toxicity towards CCD-966SK cells were obtained from CC 75% ethanol partitioned layer (CC-E). Both fractions inhibited collagenase activity, MMP-1 and MMP-3 mRNA and protein expression, as well as NF-κB activation induced by TNF-α in CCD-966SK cells. 14 compounds, which mainly consists of flavonoids and their glycosides, were isolated. Quercitrin (14.79% w/w) and quercetin (11.20% w/w) were major compounds in CC-E2 and CC-E3, respectively, as quantified by HPLC. Interestingly, both fractions also inhibited the MMP-3 protein expression synergistically, compared with treatment alone. CONCLUSION: The quantified CC fractions rich in flavonoid glycosides exhibited skin anti-aging effects via the inhibition of collagenase, MMP-1 and MMP-3 activities, probably through NF-κB pathway. This is the first study reported on MMP-1 and MMP-3 inhibitory activity of CC with its chemical profile, which revealed its potential to be developed as anti-aging products in the future.

Linoleate-pazopanib conjugation as active pharmacological ingredient to abolish hepatocellular carcinoma growth.

Small molecule compounds targeting multiple kinases involved in neoangiogenesis have shown survival benefits in patients with unresectable hepatocellular carcinoma (HCC). Nonetheless, despite the beneficial effects of multikinase inhibitors (MKIs), a lack of boosting adjuvant limits their objective response rate. Lipid conjugates have been used to improve delivery efficacy or pharmaceutical benefits for decades. However, the feasibility of utilizing lipid-drug conjugates (LDCs) in HCC regimens remains untested. In this study, oral feeding of linoleate-fluorescein isothiocyanate conjugates showed that the compound was well distributed in a spontaneous HCC mouse model. Therefore, a rationale design was developed for chemically synthesizing a linoleate-pazopanib conjugate (LAPC). The LAPC showed a significantly improved cytotoxicity compared to the parental drug pazopanib. Pazopanib's angiogenic suppressing signals were not observed in LAPC-treated HCC cells, potentially suggesting an altered mechanism of action (MOA). In an efficacy trial comparing placebo, oral pazopanib, and LAPC treatments in the hepatitis B virus transgene-related spontaneous HCC mouse model (HBVtg-HCC), the LAPC treatment demonstrated superior tumor ablating capacity in comparison to both placebo and pazopanib treatments, without any discernible systemic toxicity. The LAPC exposure is associated with an apoptosis marker (Terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) and an enhanced ferroptosis (glutathione peroxidase 4 [GPX4]) potential in HBVtg-HCC tumors. Therefore, the LAPC showed excellent HCC ablative efficacy with altered MOA. The molecular mechanisms of the LAPC and LDCs for HCC therapeutics are of great academic interest. Further comprehensive preclinical trials (e.g., chemical-manufacture-control, toxicity, distribution, and pharmacokinetics/pharmacodynamics) are expected.

Novel Aporphine- and Proaporphine-Clerodane Hybrids Identified from the Barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula with Strong Anti-DENV2 Activity.

Hybrid natural products produced via mixed biosynthetic pathways are unique and often surprise one with unexpected medicinal properties in addition to their fascinating structural complexity/diversity. In view of chemical structures, hybridization is a way of diversifying natural products usually through dimerization of two similar or dissimilar subcomponents through a C-C or N-C covalent linkage. Here, we report four structurally attractive diterpene-alkaloid conjugates polyalongarins A-D (1-4), clerodane-containing aporphine and proaporphine alkaloids, the first of its kind from the barks of Taiwanese Polyalthia longifolia (Sonn.) Thwaites var. pendula. In addition to conventional spectroscopic analysis, single crystal X-ray crystallography was employed to determine the chemical structures and stereo-configurations of 1. Compounds 1-4 were subsequently subjected to in vitro antiviral examination against DENV2 by evaluating the expression level of the NS2B protein in DENV2-infected Huh-7 cells. These compounds display encouraging anti-DENV2 activity with superb EC50 (2.8-6.4 µM) and CC50 values (50.4-200 µM). The inhibitory mechanism of 1-4 on NS2B was further explored drawing on in-silico molecular docking analysis. Based on calculated binding affinities and predicted interactions between the functional groups of 1-4 and the allosteric-site residues of the DENV2 NS2B-NS3 protease, our analysis concludes that the clerodane-aporphine/proaporphine-type hybrids are novel and effective DENV NS2B-NS3 protease inhibitors.

Chemical Composition and Chronic Toxicity of Disc-Cultured Antrodia cinnamomea Fruiting Bodies.

Antrodia cinnamomea (AC) is a popular fungus for use as folk medicine in health maintenance and disease prevention and treatment. Disc culture is a novel technique for producing AC fruiting bodies. This study aimed to investigate the bioactive components and toxicological properties of disc-cultured AC fruiting body powders (ACP) in rats. The HPLC technique was used to quantify the composition of bioactive triterpenoids in ACP. Toxicological properties were evaluated on male and female Sprague-Dawley rats receiving ACP orally at 200, 600, and 1000 mg/kg body weight for 90 days; the control group received only distilled water. The results show that ACP contained seven important AC index compounds, namely antcins A, B, C, K, and H, dehydrosulphurenic acid, and dehydroeburicoic acid. At the tested doses, oral ACP administration for 90 days caused no mortality, adverse effects on general health, body and organ weights, and food intake. Furthermore, no significant variations were observed in hematological and biochemical parameters among either sex of ACP-treated and control animals. An histopathological examination of vital organs showed no significant structural changes in organs, even in high-dose ACP-treated animals. This study indicated that ACP contained the major bioactive triterpenoids of AC fruiting bodies, and its no-observed-adverse-effect level (NOAEL) was 1000 mg/kg/day, about 20 times the recommended daily intake.

Targeting PSEN1 by lnc-CYP3A43-2/miR-29b-2-5p to Reduce ß Amyloid Plaque Formation and Improve Cognition Function.

Presenilin-1 (PSEN1) is a crucial subunit within the γ-secretase complex and regulates ß-amyloid (Aß) production. Accumulated evidence indicates that n-butylidenephthalide (BP) acts effectively to reduce Aß levels in neuronal cells that are derived from trisomy 21 (Ts21) induced pluripotent stem cells (iPSCs). However, the mechanism underlying this effect remains unclear. This article aims to investigate the possible mechanisms through which BP ameliorates the development of Alzheimer's disease (AD) and verify the effectiveness of BP through animal experiments. Results from RNA microarray analysis showed that BP treatment in Ts21 iPSC-derived neuronal cells reduced long noncoding RNA (lncRNA) CYP3A43-2 levels and increased microRNA (miR)-29b-2-5p levels. Bioinformatics tool prediction analysis, biotin-labeled miR-29b-2-5p pull-down assay, and dual-luciferase reporter assay confirmed a direct negative regulatory effect for miRNA29b-2-5p on lnc-RNA-CYP3A43-2 and PSEN1. Moreover, BP administration improved short-term memory and significantly reduced Aß accumulation in the hippocampus and cortex of 3xTg-AD mice but failed in miR-29b-2-5p mutant mice generated by CRISP/Cas9 technology. In addition, analysis of brain samples from patients with AD showed a decrease in microRNA-29b-2-5p expression in the frontal cortex region. Our results provide evidence that the LncCYP3A43-2/miR29-2-5p/PSEN1 network might be involved in the molecular mechanisms underlying BP-induced Aß reduction.

Hericium erinaceus Mycelium Ameliorates In Vivo Progression of Osteoarthritis.

Osteoarthritis (OA) is an age-related disorder that affects the joints and causes functional disability. Hericium erinaceus is a large edible mushroom with several known medicinal functions. However, the therapeutic effects of H. erinaceus in OA are unknown. In this study, data from Sprague-Dawley rats with knee OA induced by anterior cruciate ligament transection (ACLT) indicated that H. erinaceus mycelium improves ACLT-induced weight-bearing asymmetry and minimizes pain. ACLT-induced increases in articular cartilage degradation and bone erosion were significantly reduced by treatment with H. erinaceus mycelium. In addition, H. erinaceus mycelium reduced the synthesis of proinflammatory cytokines interleukin-1ß and tumor necrosis factor-α in OA cartilage and synovium. H. erinaceus mycelium shows promise as a functional food in the treatment of OA.

Antcin K inhibits VCAM-1-dependent monocyte adhesion in human rheumatoid arthritis synovial fibroblasts.

Background: Antcin K, an extract of Antrodia cinnamomea (a medicinal mushroom endemic to Taiwan commonly used in Chinese medicine preparations), inhibits proinflammatory cytokine production and angiogenesis in human rheumatoid arthritis synovial fibroblasts (RASFs), major players in RA disease. Antcin K also inhibits disease activity in mice with collagen-induced arthritis (CIA). Up until now, the effects of Antcin K upon cell adhesion molecules (CAMs) were unknown. Methods: RA and healthy synovial tissue samples (n = 10 in each group) were retrieved from the Gene Expression Omnibus (GEO) database (accession code: GDS5401) to compare CAM and monocyte marker expressions. In addition, synovial tissue samples from six RA patients and six patients undergoing arthroscopy for trauma/joint derangement (healthy controls) were subjected to immunohistochemical (IHC) analysis. mRNA and protein expression levels were analyzed in RASFs using RT-qPCR (Reverse transcription-quantitative polymerase chain reaction) and Western blot. RASFs were incubated with Antcin K and examined for monocyte adherence by fluorescence microscopy. Ankle joint tissue specimens from a CIA mouse model and healthy controls were stained with hematoxylin and eosin (H&E) and Safranin-O/Fast Green to examine histological changes and evidence of bone loss. IHC analysis determined levels of vascular cell adhesion molecule 1 (VCAM-1) and CD11b in CIA ankle tissue and clinical synovial tissue. Results: Levels of VCAM-1 expression were higher in the GEO database specimens and the study's clinical samples of RA synovial tissue compared with the healthy specimens. Antcin K dose-dependently inhibited VCAM-1 expression and monocyte adhesion in RASFs. Antcin K also significantly inhibited levels of VCAM-1 and monocyte CD11b expression in CIA tissue. These effects appeared to be mediated by MEK1/2-ERK, p38, and AP-1 signaling. Conclusions: Antcin K seems promising for the treatment of RA and deserves further investigations.

Peimine inhibits variants of SARS-CoV-2 cell entry via blocking the interaction between viral spike protein and ACE2.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several vaccines against SARS-CoV-2 have been approved; however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID-19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS-CoV-2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS-CoV-2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu-3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS-CoV-2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID-19 patients.