Alkylphthalides with intracellular triglyceride metabolism-promoting activity from the rhizomes of Cnidium officinale Makino.

Methanol extract of the Cnidium officinale Makino rhizome, which is used as a crude drug Cnidium Rhizome (Cnidii Rhizoma; "Senkyu" in Japanese) and is listed in the Japanese Pharmacopoeia XVIII, showed intracellular triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells. Thirty-five constituents, including two new alkylphthalide glycosides, senkyunosides A (1) and B (2), and a neolignan with a new stereoisomeric structure (3), were isolated in the extract. Their stereostructures were elucidated based on chemical and spectroscopic evidence. Among the isolates, several alkylphthalides, (Z)-3-butylidene-7-methoxyphthalide (9) and senkyunolides G (10), H (14), and I (15), and a polyacetylene falcarindiol (26), were found to show significant activity without any cytotoxicity at 10 µM.

Moracin D suppresses cell growth and induces apoptosis via targeting the XIAP/PARP1 axis in pancreatic cancer.

BACKGROUND: Pancreatic cancer, a tumor with a high metastasis rate and poor prognosis, is among the deadliest human malignancies. Investigating effective drugs for their treatment is imperative. Moracin D, a natural benzofuran compound isolated from Morus alba L., shows anti-inflammation and anti-breast cancer properties and is effective against Alzheimer's disease. However, the effect and mechanism of Moracin D action in pancreatic cancer remain obscure. PURPOSE: To investigate the function and molecular mechanism of Moracin D action in repressing the malignant progression of pancreatic cancer. METHODS: Pancreatic cancer cells were treated with Moracin D, and cell proliferation was evaluated by cell counting kit-8 (CCK-8) and immunofluorescence assays. The clonogenicity of pancreatic cancer cells was assessed based on plate colony formation and soft agar assay. Flow cytometry was used to detect cell apoptosis. The expression of proteins related to the apoptosis pathway was determined by Western blot analysis. Moracin D and XIAP were subjected to docking by auto-dock molecular docking analysis. Ubiquitination levels of XIAP and the interaction of XIAP and PARP1 were assessed by co-immunoprecipitation analysis. Moracin D's effects on tumorigenicity were assessed by a tumor xenograft assay. RESULTS: Moracin D inhibited cell proliferation, induced cell apoptosis, and regulated the protein expression of molecules involved in caspase-dependent apoptosis pathways. Moracin D suppressed clonogenicity and tumorigenesis of pancreatic cancer cells. Mechanistically, XIAP could interact with PARP1 and stabilize PARP1 by controlling its ubiquitination levels. Moracin D diminished the stability of XIAP and decreased the expression of XIAP by promoting proteasome-dependent XIAP degradation, further blocking the XIAP/PARP1 axis and repressing the progression of pancreatic cancer. Moracin D could dramatically improve the chemosensitivity of gemcitabine in pancreatic cancer cells. CONCLUSION: Moracin D repressed cell growth and tumorigenesis, induced cell apoptosis, and enhanced the chemosensitivity of gemcitabine through the XIAP/PARP1 axis in pancreatic cancer. Moracin D is a potential therapeutic agent or adjuvant for pancreatic cancer.

α-Viniferin, a dietary phytochemical, inhibits Monoamine oxidase and alleviates Parkinson's disease associated behavioral deficits in a mice model.

Parkinson's disease (PD) is one of the most prevalent age-related neurodegenerative disorders. Behavioral complexities worsen over time due to progressive dopaminergic (DArgic) neuronal loss at substantia nigra region of brain. Available treatments typically aim to increase dopamine (DA) levels at striatum. DA is degraded by Monoamine oxidase (MAO), thus dietary phytochemicals with MAO inhibitory properties can contribute to elevate DA levels and reduce the ailment. Characterization of naturally occurring dietary MAO inhibitors is inadequate. Based on available knowledge, we selected different classes of molecules and conducted a screening process to assess their potential as MAO inhibitors. The compounds mostly derived from food sources, broadly belonging to triterpenoids (ursane, oleanane and hopane), alkaloid, polyphenolics, monoterpenoids, alkylbenzene, phenylpropanoid and aromatic alcohol classes. Among all the molecules, highest level of MAO inhibition is offered by α-viniferin, a resveratrol trimer. Cell viability, mitochondrial morphology and reactive oxygen species (ROS) generation remained unaltered by 50 µM α-viniferin treatment in-vitro. Toxicity studies in Drosophila showed unchanged gross neuronal morphology, ROS level, motor activity or long-term survival. α-Viniferin inhibited MAO in mice brain and elevated striatal DA levels. PD-related akinesia and cataleptic behavior were attenuated by α-viniferin due to increase in striatal DA. Our study implies that α-viniferin can be used as an adjunct phytotherapeutic agent for mitigating PD-related behavioral deterioration.

Haplotype-phased genome unveils the butylphthalide biosynthesis and homoploid hybrid origin of Ligusticum chuanxiong.

Butylphthalide is one of the first-line drugs for ischemic stroke therapy, while no biosynthetic enzyme for butylphthalide has been reported. Here, we present a haplotype-resolved genome of Ligusticum chuanxiong, a long-cultivated and phthalide-rich medicinal plant in Apiaceae. On the basis of comprehensive screening, four Fe(II)- and 2-oxoglutarate-dependent dioxygenases and two CYPs were mined and further biochemically verified as phthalide C-4/C-5 desaturases (P4,5Ds) that effectively promoted the forming of (S)-3-n-butylphthalide and butylidenephthalide. The substrate promiscuity and functional redundancy featured for P4,5Ds may contribute to the high phthalide diversity in L. chuanxiong. Notably, comparative genomic evidence supported L. chuanxiong as a homoploid hybrid with Ligusticum sinense as a potential parent. The two haplotypes demonstrated exceptional structure variance and diverged around 3.42 million years ago. Our study is an icebreaker for the dissection of phthalide biosynthetic pathway and reveals the hybrid origin of L. chuanxiong, which will facilitate the metabolic engineering for (S)-3-n-butylphthalide production and breeding for L. chuanxiong.

The Effect of Salvia tomentosa Miller Extracts, Rich in Rosmarinic, Salvianolic and Lithospermic Acids, on Bacteria Causing Opportunistic Infections.

Methanolic-aqueous extracts of Salvia tomentosa Miller roots, aerial parts, and inflorescences were examined for their content of polyphenolic derivatives and the antimicrobial and cytotoxic effect. In the polyphenolic-rich profile, rosmarinic, salvianolic, and lithospermic acids along with various derivatives were predominant. A total of twenty phenolic compounds were identified using the UPLC/DAD/qTOF-MS technique. These were caffeic acid, rosmarinic acid derivatives, lithospermic acid derivatives, salvianolic acids B, F, and K derivatives, as well as sagerinic acid, although rosmarinic acid (426-525 mg/100 g of dry weight-D.W.) and salvianolic acid B (83-346.5 mg/100 g D.W.) were significantly predominant in the metabolic profile. Strong antibacterial activity of S. tomentosa extracts was observed against Staphylococcus epidermidis (MIC/MBC = 0.625 mg/mL) and Bacillus cereus (MIC = 0.312-1.25 mg/mL). The extracts showed low cytotoxicity towards the reference murine fibroblasts L929 and strong cytotoxicity to human AGS gastric adenocarcinoma epithelial cells in the MTT reduction assay. The observed cytotoxic effect in cancer cells was strongest for the roots of 2-year-old plant extracts.

Salvianolic Acid B Significantly Suppresses the Migration of Melanoma Cells via Direct Interaction with ß-Actin.

Melanoma is the most aggressive and difficult to treat of all skin cancers. Despite advances in the treatment of melanoma, the prognosis for melanoma patients remains poor, and the recurrence rate remains high. There is substantial evidence that Chinese herbals effectively prevent and treat melanoma. The bioactive ingredient Salvianolic acid B (SAB) found in Salvia miltiorrhiza, a well-known Chinese herbal with various biological functions, exhibits inhibitory activity against various cancers. A375 and mouse B16 cell lines were used to evaluate the main targets and mechanisms of SAB in inhibiting melanoma migration. Online bioinformatics analysis, Western blotting, immunofluorescence, molecular fishing, dot blot, and molecular docking assays were carried out to clarify the potential molecular mechanism. We found that SAB prevents the migration and invasion of melanoma cells by inhibiting the epithelial-mesenchymal transition (EMT) process of melanoma cells. As well as interacting directly with the N-terminal domain of ß-actin, SAB enhanced its compactness and stability, thereby inhibiting the migration of cells. Taken together, SAB could significantly suppress the migration of melanoma cells via direct binding with ß-actin, suggesting that SAB could be a helpful supplement that may enhance chemotherapeutic outcomes and benefit melanoma patients.

Screening of anti-melanoma compounds from Morus alba L.: Sanggenon C promotes melanoma cell apoptosis by disrupting intracellular Ca2+ homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. is a widespread plant that has long been considered to have remarkable medical values, including anti-inflammation in Traditional Chinese Medicine (TCM). The components of Morus Alba L. constituents have been extensively studied and have been shown to have high prospects for cancer therapy. However, limited investigations have been done on the bioactive compounds in Morus alba L. AIM OF THE STUDY: This study aimed to systematically examine the anticancer properties of 28 commercially available compounds from Morus alba L. against melanoma cells in vitro. Additionally, the anticancer mechanisms of the bioactive compound exhibiting the most significant potential were further studied. MATERIALS AND METHODS: The anti-proliferative effects of Morus alba L.-derived compounds on melanoma cells were determined by colony formation assays. Their effects on cell viability and apoptosis were determined using the CCK8 assay and flow cytometry, respectively. The binding affinity of identified Morus alba L. compounds with anticancer activities towards melanoma targets was analyzed via molecular docking. The molecular mechanism of Sanggenon C was explored using soft agar assays, EdU incorporation assays, flow cytometry, western blotting, transcriptome analysis, and xenograft assays. RESULTS: Based on colony formation assays, 11 compounds at 20 µM significantly inhibited colony growth on a panel of melanoma cells. These compounds displayed IC50 values (half maximal inhibitory concentrations) ranging from 5 µM to 30 µM. Importantly, six compounds were identified as novel anti-melanoma agents, including Sanggenon C, 3'-Geranyl-3-prenyl-2',4',5,7-tetrahydroxyflavone, Moracin P, Moracin O, Kuwanon A, and Kuwanon E. Among them, Sanggenon C showed the most potent effects, with an IC50 of about 5 µM, significantly reducing proliferation and inducing apoptosis in melanoma cells. Based on the xenograft model assay, Sanggenon C significantly inhibited melanoma cell proliferation in vivo. Sanggenon C triggered ER stress in a dose-dependent manner, which further disrupted cellular calcium ion (Ca2+) homeostasis. The Ca2+ chelator BAPTA partially restored cell apoptosis induced by Sanggenon C, confirming that Ca2+ signaling contributed to the anticancer activity of Sanggenon C against melanoma. CONCLUSIONS: In our study, 11 compounds demonstrated anti-melanoma properties. Notably, Sanggenon C was found to promote apoptosis by disrupting the intracellular calcium homeostasis in melanoma cells. This study provides valuable information for the future development of novel cancer therapeutic agents from Morus alba L.

Ultrasonic-assisted activated carbon separation removing bacterial endotoxin from salvia miltiorrhizae injection.

Ultrasonic-assisted activated carbon separation (UACS) was first employed to improve product quality by regulating adsorption rate and removing bacterial endotoxin from salvia miltiorrhizae injection. The adsorption rate was related to three variables: activated carbon dosage, ultrasonic power, and pH. With the increase of activated carbon dosage from 0.05 % to 1.0 %, the adsorption rates of salvianolic acids and bacterial endotoxin increased simultaneously. The adsorption rates at which bacteria endotoxins increased from 52.52 % to 97.16 % were much higher than salvianolic acids. As the ultrasonic power increased from 0 to 700 W, the adsorption rates of salvianolic acids on activated carbon declined to less than 10 %, but bacterial endotoxin increased to more than 87 %. As the pH increased from 2.00 to 8.00, the adsorption rate of salvianolic acid dropped whereas bacterial endotoxin remained relatively stable. On the basis of response surface methodology (RSM), the optimal separation conditions were established to be activated carbon dose of 0.70 %, ultrasonic power of 600 W, and pH of 7.90. The experimental adsorption rates of bacterial endotoxin were 94.15 %, which satisfied the salvia miltiorrhizae injection quality criterion. Meanwhile, salvianolic acids' adsorption rates were 1.92 % for tanshinol, 4.05 % for protocatechualdehyde, 2.21 % for rosmarinic acid, and 3.77 % for salvianolic acid B, all of which were much lower than conventional activated carbon adsorption (CACA). Salvianolic acids' adsorption mechanism on activated carbon is dependent on the component's molecular state. Under ideal separation conditions, the molecular states of the four salvianolic acids fall between 1.13 % and 6.60 %. The quality of salvia miltiorrhizae injection can be improved while maintaining injection safety by reducing the adsorption rates of salvianolic acids to less than 5 % by the use of ultrasound to accelerate the desorption mass transfer rate on the activated carbon surface. When activated carbon adsorption was used in the process of producing salvia miltiorrhizae injection, the pH of the solution was around 5.00, and the proportion of each component's molecular state was tanshinol 7.05 %, protocatechualdehyde 48.93 %, rosmarinic acid 13.79 %, and salvianolic acid B 10.28 %, respectively. The loss of useful components was evident, and the corresponding activated carbon adsorption rate ranged from 20.74 % to 41.05 %. The average variation rate in plasma His and IgE was significant (P < 0.05) following injection of 0.01 % activated carbon, however the average variation rate of salvia miltiorrhizae injection was dramatically decreased with the use of UACS and CACA (P > 0.05). The ultrasonic at a power intensity of 60 W/L and the power density of 1.20 W/cm2 may resolve the separation contradiction between salvianolic acids and bacterial endotoxin, according to experiments conducted with UACS at different power intensities. According to this study, UACS has a lot of potential applications in the pharmaceutical manufacturing industry and may represent a breakthrough in the field of ultrasonic separation.

Synergistic effects and molecular mechanisms of DL-3-n-butylphthalide combined with dual antiplatelet therapy in acute ischemic stroke.

DL-3-n-butylphthalide (NBP) is isolated from the seeds of Apium graveolens L., and has been recently used as a neuroprotective agent for acute ischemic stroke. The present study aimed to determine the efficacy and safety of the combined use of dual antiplatelet therapy (DAPT) and NBP for treating of acute ischemic stroke in rats and to explore the synergistic mechanism of this treatment strategy in rat middle cerebral artery occlusion models. The efficacy of DAPT combined with NBP was evaluated by determining neurological deficits, infarction status, and histological changes. Changes in body weight, blood glucose level, blood count, and serum biochemical parameters were detected to evaluate the safety. To explore the synergistic pharmacological mechanism, the mRNA expression and protein levels of key proteins in the pyroptosis-inflammatory pathway, and the pyroptosis ratio of microglias were examined. Compared with the administration of NBP or DAPT alone, combination of them significantly improved neurological deficits, reduced infarct area, and repaired tissue injury and inflammation after cerebral ischemia. No hepatorenal toxicity was observed. The mRNA expression and protein levels of key proteins in the pyroptosis-inflammation pathway, and the pyroptosis ratio of microglias were significantly downregulated in the combined administration group than in the monotherapy group. We demonstrated that the combined use of NBP and DAPT exhibits better efficacy and high safety and plays a synergistic role by inhibiting the pyroptosis-inflammation pathway in the brain tissues, particularly in microglial cells.

Inhibition of glycolysis and SIRT1/GLUT1 signaling ameliorates the apoptotic effect of Leptosidin in prostate cancer cells.

Since the silent information regulation 2 homolog-1 (sirtuin, SIRT1) and glucose transporter 1 (GLUT1) are known to modulate cancer cell metabolism and proliferation, the role of SIRT1/GLUT1 signaling was investigated in the apoptotic effect of Leptosidin from Coreopsis grandiflora in DU145 and PC3 human prostate cancer (PCa) cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis, Western blotting, cBioportal correlation analysis, and co-immunoprecipitation were used in this work. Leptosidin showed cytotoxicity, augmented sub-G1 population, and abrogated the expression of pro-poly (ADP-ribose) polymerase (pro-PARP) and pro-cysteine aspartyl-specific protease (pro-caspase3) in DU145 and PC3 cells. Also, Leptosidin inhibited the expression of SIRT1, GLUT1, pyruvate kinase isozymes M2 (PKM2), Hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA) in DU145 and PC3 cells along with disrupted binding of SIRT1 and GLUT1. Consistently, Leptosidin curtailed lactate, glucose, and ATP in DU145 and PC3 cells. Furthermore, SIRT1 depletion enhanced the decrease of GLUT1, LDHA, and pro-Cas3 by Leptosidin in treated DU145 cells, while pyruvate suppressed the ability of Leptosidin in DU145 cells. These findings suggest that Leptosidin induces apoptosis via inhibition of glycolysis and SIRT1/GLUT1 signaling axis in PCa cells.

3D bioprinting of Salvianolic acid B-sodium alginate-gelatin skin scaffolds promotes diabetic wound repair via antioxidant, anti-inflammatory, and proangiogenic effects.

In patients with diabetic wounds, wound healing is impaired due to the presence of persistent oxidative stress, an altered inflammatory response, and impaired angiogenesis and epithelization. Salvianolic acid B (SAB), which is derived from the Chinese medicinal plant Salvia miltiorrhiza, has been found to exhibit antioxidant, anti-inflammatory, and proangiogenic effects. Previous studies have used 3D bioprinting technology incorporating sodium alginate (SA) and gelatin (Gel) as basic biomaterials to successfully produce artificial skin. In the current study, 3D bioprinting technology was used to incorporate SAB into SA-Gel to form a novel SAB-SA-Gel composite porous scaffold. The morphological characteristics, physicochemical characteristics, biocompatibility, and SAB release profile of the SAB-SA-Gel scaffolds were evaluated in vitro. In addition, the antioxidant, anti-inflammatory, and proangiogenic abilities of the SAB-SA-Gel scaffolds were evaluated in cells and in a rat model. Analysis demonstrated that 1.0 wt% (the percentage of SAB in the total weight of the solution containing SA and Gel) SAB-SA-Gel scaffolds had strong antioxidant, anti-inflammatory, and proangiogenic properties both in cells and in the rat model. The 1.0% SAB-SA-Gel scaffold reduced the expression of tumor necrosis factor-α, interleukin-6, and interluekin-1ß and increased the expression of transforming growth factor-ß. In addition, this scaffold removed excessive reactive oxygen species by increasing the expression of superoxide dismutase, thereby protecting fibroblasts from injury. The scaffold increased the expression of vascular endothelial growth factor and platelet/endothelial cell adhesion molecule-1, accelerated granulation tissue regeneration and collagen deposition, and promoted wound healing. These findings suggest that this innovative scaffold may have promise as a simple and efficient approach to managing diabetic wound repair.

Salvianolic acid B protects against pulmonary fibrosis by attenuating stimulating protein 1-mediated macrophage and alveolar type 2 cell senescence.

Idiopathic pulmonary fibrosis (IPF), as the most common idiopathic interstitial pneumonia, is caused by a complex interaction of pathological mechanisms. Interestingly, IPF frequently occurs in the middle-aged and elderly populations but rarely affects young people. Salvianolic acid B (SAB) exerts antioxidant, antiinflammatory, and antifibrotic bioactivities and is considered a promising drug for pulmonary disease treatment. However, the pharmacological effects and mechanisms of SAB on cellular senescence of lung cells and IPF development remain unclear. We used bleomycin (BLM)-induced pulmonary fibrosis mice and different lung cells to investigate the antisenescence impact of SAB and explain its underlying mechanism by network pharmacology and the Human Protein Atlas database. Here, we found that SAB significantly prevented pulmonary fibrosis and cellular senescence in mice, and reversed the senescence trend and typical senescence-associated secretory phenotype (SASP) factors released from lung macrophages and alveolar type II (AT2) epithelial cells, which further reduced lung fibroblasts activation. Additionally, SAB alleviated the epithelial-mesenchymal transition process of AT2 cells induced by transforming growth factor beta. By predicting potential targets of SAB that were then confirmed by chromatin immunoprecipitation-qPCR technology, we determined that SAB directly hampered the binding of transcription factor stimulating protein 1 to the promoters of SASPs (P21 and P16), thus halting lung cell senescence. We demonstrated that SAB reduced BLM-induced AT2 and macrophage senescence, and the subsequent release of SASP factors that activated lung fibroblasts, thereby dual-relieving IPF. This study provides a new scientific foundation and perspective for pulmonary fibrosis therapy.

Co-assembled Supramolecular Hydrogel of Salvianolic Acid B and a Phosphopeptide for Enhanced Wound Healing.

Supramolecular natural product gels (NPGs) have emerged as promising biomaterials for scalable and adjustable drug delivery systems. These gels possess biocompatibility, biodegradability, and the ability to mimic the extracellular matrix. Salvianolic acid B (SAB), derived from Salvia miltiorrhiza, a Chinese medicinal plant, exhibits various beneficial properties such as antioxidant, antifibrotic, and angiogenic effects. In our research, we serendipitously discovered that the co-assembly of SAB and a soluble phosphopeptide results in the formation of a robust and adhesive hydrogel termed 1&SAB hydrogel. This hydrogel effectively prolongs the retention time of the therapeutic agents on the skin's wound surface, thereby promoting wound healing. The hydrogel demonstrates antioxidant effects, enhances cell migration, accelerates angiogenesis, and inhibits scar hyperplasia. This innovative gel material offers a simple and efficient approach to managing skin wounds and holds promise for application in complex wound-healing treatments.

Spiro-Flavonoids in Nature: A Critical Review of Structural Diversity and Bioactivity.

Based on the literature data from 1973 to 2022, this work summarizes reports on spiro-flavonoids with a spiro-carbon at the center of their structure and how this affects their isolation methods, stereochemistry, and biological activity. The review collects 65 unique structures, including spiro-biflavonoids, spiro-triflavonoids, spiro-tetraflavonoids, spiro-flavostilbenoids, and scillascillin-type homoisoflavonoids. Scillascillin-type homoisoflavonoids comprise spiro[bicyclo[4.2.0]octane-7,3'-chromane]-1(6),2,4-trien-4'-one, while the other spiro-flavonoids contain either 2H,2'H-3,3'-spirobi[benzofuran]-2-one or 2'H,3H-2,3'-spirobi[benzofuran]-3-one in the core of their structures. Spiro-flavonoids have been described in more than 40 species of eight families, including Asparagaceae, Cistaceae, Cupressaceae, Fabaceae, Pentaphylacaceae, Pinaceae, Thymelaeaceae, and Vitaceae. The possible biosynthetic pathways for each group of spiro-flavonoids are summarized in detail. Anti-inflammatory and anticancer activities are the most important biological activities of spiro-flavonoids, both in vitro and in vivo. Our work identifies the most promising natural sources, the existing challenges in assigning the stereochemistry of these compounds, and future research perspectives.

Herpetin Promotes Bone Marrow Mesenchymal Stem Cells to Alleviate Carbon Tetrachloride-Induced Acute Liver Injury in Mice.

Herpetin, an active compound derived from the seeds of Herpetospermum caudigerum Wall., is a traditional Tibetan herbal medicine that is used for the treatment of hepatobiliary diseases. The aim of this study was to evaluate the stimulant effect of herpetin on bone marrow mesenchymal stem cells (BMSCs) to improve acute liver injury (ALI). In vitro results showed that herpetin treatment enhanced expression of the liver-specific proteins alpha-fetoprotein, albumin, and cytokeratin 18; increased cytochrome P450 family 3 subfamily a member 4 activity; and increased the glycogen-storage capacity of BMSCs. Mice with ALI induced by carbon tetrachloride (CCl4) were treated with a combination of BMSCs by tail-vein injection and herpetin by intraperitoneal injection. Hematoxylin and eosin staining and serum biochemical index detection showed that the liver function of ALI mice improved after administration of herpetin combined with BMSCs. Western blotting results suggested that the stromal cell-derived factor-1/C-X-C motif chemokine receptor 4 axis and the Wnt/ß-catenin pathway in the liver tissue were activated after treatment with herpetin and BMSCs. Therefore, herpetin is a promising BMSC induction agent, and coadministration of herpetin and BMSCs may affect the treatment of ALI.

[Protective mechanism of salvianolic acid B on blood vessels].

Salvianolic acid B(Sal B) is the main water-soluble component of Salvia miltiorrhiza Bunge. Studies have found that Sal B has a good protective effect on blood vessels. Sal B can protect endothelial cells by anti-oxidative stress, inducing autophagy, inhibiting endoplasmic reticulum stress(ERS), inhibiting endothelial inflammation and adhesion molecule expression, inhibiting endothelial cell permeability, anti-thrombosis, and other ways. In addition, Sal B can alleviate endothelial cell damage caused by high glucose(HG). For vascular smooth muscle cell(VSMC), Sal B can reduce the synthesis and secretion of inflammatory factors by inhibiting cyclooxygenase. It can also play a vasodilatory role by inhibiting Ca~(2+) influx. In addition, Sal B can inhibit VSMC proliferation and migration, thereby alleviating vascular stenosis. Sal B also inhibits lipid deposition in the subendothelium, inhibits macrophage conversion to foam cells, and reduces macrophage apoptosis, thereby reducing the volume of subendothelial lipid plaques. For some atherosclerosis(AS) complications, such as peripheral artery disease(PAD), Sal B can promote angiogenesis, thereby improving ischemia. It should be pointed out that the conclusions obtained from different experiments are not completely consistent, which needs further research. In addition, previous pharmacokinetics showed that Sal B was poorly absorbed by oral administration, and it was unstable in the stomach, with a large first-pass effect in the liver. Sal B had fast distribution and metabolism in vivo and short drug action time. These affect the bioavailability and biological effects of Sal B, and the development of clinically valuable Sal B non-injectable delivery systems remains a great challenge.

Discovery of a triphenylamine-benzofuran derivative as fluorescent probe for hydrogen polysulfide in tea samples.

In this work, a novel triphenylamine-benzofuran derived fluorescent probe, TBF-SS, was developed for detecting hydrogen polysulfide in tea samples and intracellular imaging. TBF-SS showed the practical advantages including high sensitivity (LOD = 0.01 µM), high selectivity, rapid response (within 15 min), and steadiness in various environmental conditions. The detecting system was steady within pH range of 6.0-11.0 and temperature range of 20-55 °C. The probe TBF-SS could guarantee the stable detection of H2Sn for 7 d in storage of either solid or solution. In particular, in the application of various tea samples with different brewing times and testing temperatures, the recovery percentages varied in the range of 95.22 % to 105.0 %. Therefore accurate monitoring of H2Sn could be achieved by using the probe TBF-SS. In addition, TBF-SS could monitor the exogenous level, the ß-lapachone-induced generation and the tea-sample-treated introduction of H2Sn in living MCF-7 cells. This work might inspire the improvement of the serviceability of fluorescent implements.

Virtual screening and computational simulation analysis of antimicrobial photodynamic therapy using propolis-benzofuran A to control of Monkeypox.

BACKGROUND: Monkeypox is a viral zoonotic disease and there are no available treatments that specifically target the monkeypox virus. Antimicrobial photodynamic therapy (aPDT) is a non-invasive approach that has been introduced as a targeted adjuvant treatment against various microbial infections. In this study, we used a computational strategy to investigate the potential of aPDT using propolis-benzofuran A against the Monkeypox virus. METHODS: In this in silico study, the evaluation of drug-likeness, molecular properties, and bioactivity of propolis-benzofuran A was carried out using SwissADME. Pro-Tox II and OSIRIS servers were used to identify the organ toxicities and toxicological endpoints of propolis-benzofuran A. Molecular docking approach was employed to screen the potential binding modes of propolis-benzofuran A ligand with the Monkeypox virus A48R protein (PDB ID: 2V54). RESULTS: The results of the computational investigation revealed that propolis-benzofuran A obeyed all the criteria of Lipinski's rule of five and exhibited drug-likeness. The photosensitizing agent tested was categorized as toxicity class-5 and was found to be non-hepatotoxic, non-carcinogenic, non-mutagenic, and non-cytotoxic. The docking studies employing a predicted three-dimensional model of Monkeypox virus A48R protein with propolis-benzofuran A ligand exhibited good binding affinity (-7.84 kcal/mol). DISCUSSION: The computational simulation revealed that propolis-benzofuran A had a strong binding affinity with the Monkeypox virus A48R protein. Hence, aPDT based on this natural photosensitizer can be proposed as an adjuvant treatment against the Monkeypox virus.

A new benzofuran compound from the resinous exudates of Commiphora myrrha.

A new benzofuran derivative, identified as myrrhain A (1), was isolated from the resinous exudates of Commiphora myrrha, together with the four known compounds: commipharane (2), myrrhterpeniod (3), myrrhone (4), and 9-methoxymyrrhone (5). All structures were elucidated by NMR and MS analyses. DPPH assay of compounds 1-5 revealed for the first time that all of them possess moderate antioxidative activity.

Advances in Research on Bioactivity, Toxicity, Metabolism, and Pharmacokinetics of Usnic Acid In Vitro and In Vivo.

Lichens are among the most widely distributed plants on earth and have the longest growth cycle. Usnic acid is an abundant characteristic secondary metabolite of lichens and the earliest lichen compound used commercially. It has diverse pharmacological activities, such as anti-inflammatory, antibacterial, antiviral, anticancer, antioxidant, and photoprotective effects, and promotes wound healing. It is widely used in dietary supplements, daily chemical products (fodder, dyes, food, perfumery, and cosmetics), and medicine. However, some studies have found that usnic acid can cause allergic dermatitis and drug-induced liver injury. In this paper, the bioactivity, toxicity, in vivo and in vitro metabolism, and pharmacokinetics of usnic acid were summarized. The aims were to develop and utilize usnic acid and provide reference for its future research.