Visible-light photoredox-catalyzed sulfidation reactions with elemental sulfur have emerged as a mild and attractive strategy to construct sulfur-containing compounds in organic synthetic chemistry. Herein, visible-light-induced pyridylphosphination of alkenes with 4-cyanopyridines, secondary phosphines, and elemental sulfur leading to beta-pyridylalkylated phosphine sulfides has been developed. The present photocatalytic pyridylphosphination reaction can incorporate both pyridine and phosphine sulfide structural units into the same molecular framework under mild conditions by using elemental sulfur as sulfur source, in which P=S, C-P, and C-C bonds were successfully constructed in a single operation. A preliminary mechanistic investigation shows that diphenylphosphine sulfide might be the key intermediate and a photocatalytic phosphonyl radical-participated process was involved in this transformation. This visible-light-promoted protocol has the advantages of clean energy source, mild condition, broad substrate scope and good compatibility of functional groups.

A visible-light-induced pyridylation-thioesterification of alkenes with 4-cyanopyridines and thioacids has been developed. This transformation could provide a series of structurally diverse β-pyridyl-thioesters in moderate to good yields at room temperature. The advantages of this protocol are highlighted by its characteristics of clean energy source, mild conditions, and good compatibility of functional groups. Notably, β-pyridyl-thioesters have exhibited significant inhibitory activities against human hepatoma cell line (HepG2).

A visible-light-promoted four-component reaction of α-diazoesters, cyclic ethers, elemental sulfur, and secondary phosphines has been developed. This multicomponent reaction proceeded under mild conditions to afford a range of dithiophosphinates using elemental sulfur as the sulfur source. The present photochemical protocol offers a sustainable and practical strategy for dithiophosphinate synthesis without transition metals or complex operational procedures.

A simple and efficient strategy has been developed for the synthesis of organic thiocyanates through direct ring-opening thiocyanation reactions of aryl, alkenyl, and alkynyl sulfonium ylides using elemental sulfur and TMSCN. Using elemental sulfur as the sulfur source, this transformation proceeds under mild conditions without the need for metal reagents or malodorous materials. Notably, this approach features excellent versatility, as evidenced by its compatibility with scale-up synthesis and the late-stage modification of the corresponding products.

A visible-light-induced oximo-thioesterification of alkenes with tert-butyl nitrite and thioacids leading to the formation of α-thioester oximes has been developed. This transformation provides a series of diverse α-thioester oximes in moderate to good yields at room temperature. The present photocatalytic protocol has the advantages of metal-free condition, simple operation, green energy source, and favorable functional group tolerance.

A supramolecular network has been successfully constructed via synergistic coordination and host-guest interactions, achieving an efficient two-step FRET cascade.

Reducing postprandial blood glucose (PBG) constitutes a core objective in the clinical management of diabetes mellitus. Urtica cannabina L., a traditional medicinal and edible homologous plant, is widely distributed in China; however, research on its pharmacological activity and chemical composition remains relatively scarce. In the present study, the PBG-lowering potential of U. cannabina L. was confirmed both in vitro and in vivo, and its chemical constituents were preliminarily identified by UPLC-triple-TOF-MS/MS for the first time. Notably, acarbose (8 mg/kg), a clinically approved first-line α-glucosidase inhibitor, and UCE20 (20% ethanol extract of U. cannabina L.) at 10 mg/kg both significantly reduced PBG levels. Furthermore, UPLC-triple-TOF MS/MS analysis combined with correlation analysis has preliminarily indicated that hydroxycinnamoyl quinates and flavonoid C-glycosides may serve as the primary bioactive components responsible for the PBG-lowering effect. These findings suggested U. cannabina L. holds potential as a medicinal ingredient or health food to assist in the regulation of PBG levels.

A simple and efficient oximophosphinothiolation of alkenes with sodium nitrite, elemental sulfur, and secondary arylphosphines has been developed. This transformation can be carried out under mild and additive-free conditions, employing NaNO2 and S8 as the NO source and sulfur source, respectively. A wide variety of α-dithiophosphinate oximes could be accessed via this method in moderate to good yields, and the reaction showed good tolerance to diverse functional groups.

Nitraria tangutorum Bobr. (NTB), mainly distributed in the Qaidam Basin, had high medicinal and ecological value, and research on its chemical components and bioactivities is necessary. In this study, three novel β-carboline alkaloids tangutorid LI-III were isolated and tentatively identified from NTB fruit, which represent the first example of coumaroyl glucoside-derived β-carboline alkaloids isolated from natural products. The possible biogenetic pathways and MS/MS fragmentation forms of tangutorid LI-III were also tentatively speculated, which provide theoretical basis for rapid identification of this type of components. Hypoglycemic activity research of isolated compounds confirmed that depsides (dihydroxybenzoyl-trihydroxyphenylmethylacetate, 14) not only had strong sucrase and maltase inhibitory activities, but also exhibited noteworthy insulin resistance (IR) ameliorative effects. In addition, cyclic dipeptide (cyclo (tyr-tyr), 10) was also demonstrated to have significant IR improvement effect. This study enriched the structural types of β-carboline alkaloids in fruits and expanded the biological activity of cyclic dipeptide and depsides.

An efficient strategy for the construction of α-keto thioesters has been developed via photocatalytic one-pot three-component reaction of sulfoxonium ylides with elemental sulfur and α-ketoacids. The reaction proceeded smoothly at room temperature using elemental sulfur as a sulfurizing agent and generated a series of α-keto thioesters in moderate to good yields. The present photocatalyzed transformation involves a carbonyl thiyl radical-based thioester synthesis, which overcomes traditional methods that employ unstable and malodorous thiols or thioacids.

A visible-light-induced difunctionalization of alkenes with quinoxalin-2(1H)-ones and thioacids has been developed at room temperature. The present protocol, which utilizes 4CzIPN as the photocatalyst and K3PO4 as base, provides a series of structurally diverse thioester-containing quinoxalin-2(1H)-ones in moderate to good yields. This transformation undergoes through a radical pathway with the simultaneous installation of thioester and quinoxalin-2(1H)-one into one structural framework.

ETHNOPHARMACOLOGICAL RELEVANCE:The incidence of cholestatic liver disease (CLD), which is primarily marked by abnormal bile acids (BAs) metabolism and can result in significant hepatic injury, is rising. Nevertheless, there remains a lack of effective treatments and drugs in clinical practice. Silphium perfoliatum L. (SP) is rich in various structural types of caffeoylquinic acid (CQA) compounds, and it is a traditional herb of North American Indians with hepatobiliary therapy effects. However, its therapeutic effect and mechanism of action on CLD have never been studied. AIM OF THE STUDY:To determine if SP-8, an extract rich in CQAs from SP, protects against cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) and to clarify its mechanism based on the farnesoid x receptor (FXR) signaling pathway and enterohepatic circulation of BAs. MATERIALS AND METHODS:The therapeutic efficacy of SP-8 was evaluated by assessing the serum biochemical indices, inflammatory factors, and liver histopathology. Targeted metabolomics of the BAs was studied in the feces, liver, serum, and bile using UPLC-MS/MS. Additionally, a Western blot analysis was used to examine the expression levels of the peroxisome proliferator-activated receptor γ (PPARγ), the FXR, and proteins related to the synthesis and transport of BAs. 16S rRNA gene sequencing was performed to evaluate the gut microbiota (GM). Finally, molecular docking simulations were conducted to assess the interaction between seven types of CQAs from SP-8 with FXR and PPARγ. RESULTS:SP-8 significantly enhanced the health status of cholestatic mice induced by ANIT as evidenced by a notable reduction in the liver function indices and pro-inflammatory factors, restoration of liver pathological damage, and acceleration of BAs excretion through the feces. In addition, the levels of harmful secondary BAs in the liver and blood were significantly reduced by SP-8. Furthermore, the results of the study on the mechanism of action confirmed that SP-8 not only regulated FXR and PPARγ but also significantly ameliorated the GM structure, thereby promoting the enterohepatic circulation of BAs and achieving the homeostasis of the BAs in the blood and liver. In addition, SP-8 successfully reduced the inflammatory response by strongly suppressing the nuclear translocation of NF-κBp65. According to the molecular docking results, the extract's primary active ingredients could be the seven CQAs in SP-8, as they exhibited a strong affinity for both FXR and PPARγ. Finally, the Mantel test analysis revealed a significant correlation among cholestatic-associated parameters, the GM, and BAs. CONCLUSION:It was confirmed for the first time that the SP-8 extract of Silphium perfoliatum L. that is rich in seven CQAs had a strong therapeutic effect on ANIT-induced CLD. Its mechanism may involve the regulation of the FXR signaling pathway and the amelioration of the GM structure to promote the homeostasis of BAs enterohepatic circulation. This study provides a potential candidate medicinal herb and its components for the development of CLD therapeutic drugs.

Background: Reducing postprandial blood glucose (PBG) is a crucial strategy for treating diabetes and minimizing the risk of complications. Developing efficient and safe α-glycosidase inhibitors from natural products to lower PBG has attracted much attention. Silphium perfoliatum L. (SP), a traditional herbal medicine of North American Indigenous tribes, has efficacy of treating metabolic diseases, but its hypoglycemic activity and bioactive components have not been fully studied. Methods: In vitro α-glucosidase inhibition and in vivo sucrose/maltose/starch tolerance assays were performed to assess the hypoglycemic effects of SP extracts, and UPLC-Triple-TOF-MS/MS analysis was used to tentatively identify its chemical structure composition. In vitro enzyme inhibition and molecular docking were used to verify the effective ingredients. Results: In vitro hypoglycemic activities of four extracts of SP (SP-10/SP-40/SP-60/SP-C) showed that SP-10 exhibited strong α-glucosidase (sucrase and maltase) inhibitory effects with IC50 of 67.81 μg/mL and 62.99 μg/mL, respectively. Carbohydrate tolerance assays demonstrated that SP-10 could significantly reduce the PBG levels of diabetic mice, with a significant hypoglycemic effect at a dosage of 20 mg/kg. A total of 26 constituents, including 11 caffeoylquinic acids (CQAs) and 15 flavonol glycosides, were tentatively identified by mainly analyzing secondary MS fragmentation. Moreover, three CQAs rich in SP-10, namely chlorogenic acid (CGA), neochlorogenic acid (NCGA), and cryptochlorogenic acid (CCGA), may be the main hypoglycemic substances, as evidenced by their inhibitory effects on sucrase and maltase. Conclusions: The α-glucosidase inhibitory effects of SP extract both in vitro and in vivo and its active ingredients were systematically studied for the first time. Results indicated that SP extract, rich in CQAs, had significant hypoglycemic activity, supporting the considerable potential of SP as hypoglycemic functional food or cost-effective therapeutic agents for diabetes treatment.

Four new Euphorbia diterpenoids, helioranes A-C (1-3) and heliophane A (4), and six know analogues were isolated from the whole plants of Euphorbia helioscopia. Among them, compounds 1-3 are typical lathyranes varying with substituents, compound 4 is a rare 7,8-seco-jatrophane diterpenoid. The structures of the novel compounds were unequivocally established through an integrated approach combining spectroscopic analyses and quantum chemical calculations. Lipid-lowering activity screening in 3 T3-L1 cells demonstrated that compound 3 and 9 exhibited potential inhibitory effects on lipid accumulation.

Visible-light induced multi-component carbonthioesterification reaction of alkenes with quinoxalin-2(1H)-ones, elemental sulfur and α-ketoacids has been developed. The present transformation is conducted under mild conditions to afford a wide range of biologically important quinoxalin-2(1H)-one-containing thioesters in moderate to good yields. Interestingly, the formed products show the potency of antitumor activities against HepG2. A mechanistic investigation indicates that carbonyl thiyl radical is formed through the coupling of photocatalytic activated elemental sulphur with acyl radical derived from decarboxylation of α-ketoacids.

A simple and efficient strategy has been developed to access β-oximino phosphorodithioate through additive-free four-component reactions of sodium nitrite, aromatic alkenes, P4S10, and alcohols. The present reaction was carried out under mild conditions through a positive ion process. A series of β-oximino phosphorodithioates could be obtained in moderate to good yields by employing sodium nitrite as a promoter and an oxime source.

A visible-light photoredox-catalyzed strategy has been developed for the synthesis of δ-keto esters through alkylation/1,2-aryl migration of allylic alcohols with malonic esters. This transformation could be undergone at room temperature in a step- and atom-economic manner by using Eosin Y and air as a metal-free photocatalyst and green oxidant, respectively. Preliminary mechanistic analysis suggested that 1,2-aryl migration proceeded through a radical process.

β-HgS as the main component of Tibetan medicine Zuotai (ZT) is widely used in the treatment of central nervous system diseases. Although the synergism of HgS has been clinically verified for more than 2000 years, its synergetic mechanism is still an unsolved mystery and a huge challenge. Notably, we clearly and intuitively demonstrate that Zuotai or β-HgS is auto-synthesized by organisms into spherical HgS nanoparticles with protein corona, with an overall particle size of 30–195 nm and a core of HgS NPs of 5–7 nm. Further research showed that HgS NPs facilitated the transport of Oxiracetam (ORT), Memantine Hydrochloride (MH) and Entinostat (MS-275) across the blood-brain barrier (BBB), especially the brain accumulation of MS-275 increased by more than three times. Meanwhile, HgS NPs enhanced the effect of MS-275 on spatial learning and memory ability of APP/PS1 mice. Further studies confirmed that HgS NPs increased the permeability of the blood-brain barrier (BBB) by regulating endocytosis (Upregulation of caveolin, clathrin, and dynamin, downregulation P-gp) thereby facilitate the transport of drugs across BBB with more than threefold higher brain accumulation and long-lasting efficiency enhancement (4 days). Our findings reveal that these in vivo-generated HgS NPs provide an efficient, convenient, and biocompatible drug delivery platform for crossing the BBB. Importantly, our findings offer new hopes and ideas for in-depth research on highly valuable and mysterious metal preparations in classic Chinese and Tibetan medicine.