Introduction: Hedysarum alpinum L. (HA) contains considerable amounts of polyphenols and saponins, and exhibits immune-enhancing and antiviral properties. Evidence indicates that triterpenoid saponins possess neuroprotective effects against neurodegenerative damage. The present study evaluated the effect of an HA saponin-rich n-butanol fraction (HABF) on cognitive deficits induced by scopolamine in a rat model. Methods: Cognitive impairment was assessed using passive avoidance (PA) and novel object recognition (NOR) tasks. Total triterpene saponins of HABF were quantified by the colorimetric method using oleanolic acid as a standard compound. Biochemical analyses of hippocampus tissue included measurements of acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT), catalase (CAT), and tumor necrosis factor-α (TNF-α). Results: HABF contained 131 ± 0.02 mg oleanolic acid equivalent (OAE)/g of total triterpene saponins. Scopolamine significantly impaired memory, as shown by a decreased discrimination index in the NOR test and reduced retention latency in the PA test. Pretreatment with HABF (40 and 80 mg/kg) significantly alleviated the memory deficits in both tasks. Scopolamine significantly increased AChE activity and TNF-α levels, and decreased CAT activity compared to the vehicle-treated group. These alterations were significantly reversed by HABF treatment, whereas ChAT activity remained unchanged compared with the MPTP-treated group. Conclusion: HABF, rich in triterpene saponins, ameliorates scopolamine-induced memory impairment, likely through the inhibition of AChE activity and modulation of oxidative stress and inflammation. These findings may suggest its potential neuroprotective effect in cognitive dysfunction.

Gene therapy holds significant promise for the treatment of liver cancer. However, the development of safe and efficient gene delivery systems remains a critical challenge. Cationic polymers are widely utilized as gene carriers due to their high transfection efficiency, yet their application is often hindered by cytotoxicity and lack of target specificity. In this study, we present a one-step strategy to conjugate glycyrrhetinic acid (GA) to cationic polymers, aiming to reduce cytotoxicity and enhance liver-specific targeting. A series of GA-modified polyamidoamine (PPI) dendrimers were synthesized by varying the degree of GA substitution and were comprehensively characterized. The resulting GA-PPI dendrimers exhibited strong plasmid DNA (pDNA) binding and protection capabilities, forming stable GA-PPI/pDNA polyplexes. Notably, GA-PPI dendrimers with 5.10% GA substitution achieved a 5.1-fold enhancement in hepatocyte transfection efficiency (22.7% vs. 4.45% for unmodified PPI), while maintaining high cell viability (97.8% vs. 76.4%). In vivo, GA-PPI-3/pDNA polyplexes demonstrated superior antitumor efficacy in HepG2 xenograft models. These results underscore the potential of GA-functionalized PPI dendrimers as an effective and safe platform for targeted gene therapy in hepatocellular carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE:Liver fibrosis involves changes in tissue structure and extracellular matrix composition due to multiple chronic liver diseases. Hepatic stellate cells (HSCs) play a crucial role in the development of liver fibrosis. Allii Tuberosi Semen, derived from the mature seed of Allium tuberosum Rottl.ex Spreng. (Liliaceae), is a traditional Chinese medicine known for its numerous bioactive properties, including hepatoprotective effects, sexual function improvement, immunity enhancement, anti-oxidation, and anti-microbial activities. AIM OF THE STUDY:This study aimed to identify effective ingredients in Allii Tuberosi Semen with anti-liver fibrosis properties. MATERIALS AND METHODS:Extensive spectroscopic analysis was performed to identify the structures of the unreported compounds. Furthermore, these compounds were evaluated for anti-fibrotic effects on HSCs and the underlying molecular mechanisms. RESULTS:Five new steroidal saponins, compounds 1-5, were isolated from Allii Tuberosi Semen, together with eight known compounds. Additionally, the carbon and hydrogen signals of compound 6 were assigned for the first time. These compounds significantly suppressed TGF-β1-induced HSCs activation via effectively reducing cell viability and migration while increasing the apoptosis rate. Further investigation was found that compound 8 inhibit the TGF-β1/Smad and PI3K/Akt pathways, increasing Bax/Bcl-2 ratio. CONCLUSIONS:The results indicate that compounds 1-12 are effective inhibitors of liver fibrosis, making them promising agents for treating hepatic fibrosis.

Mesua ferrea L. was commonly used in Uyghur medicine, and the flowering buds of M. ferrea extract exhibited significant inhibitory effects on the proliferation of breast cancer cells in our preliminary research; however, the underlying active components remain to be elucidated. In this study, firstly, we extracted the flowering buds of M. ferrea with methanol and obtained eleven bioactive sub-fractions (MF-P-1-MF-P-11), and MF-P-5 showed the strongest inhibitory activity against MDA-MB-231 and 4T1 cells. Subsequently, 52 compounds from MF-P-5 were identified by UPLC Q-TOF MS/MS. In addition, ten compounds (MF1-MF10) from MF-P-5 were separated and identified, and MF5 could inhibit MDA-MB-231 and 4T1 cells proliferation as MTT and colony formation assay, suppress the migration of MDA-MB-231 and 4T1 cells by means of wound healing assay, reduce the expression level of E-cadherin, and induce MDA-MB-231 and 4T1 cells apoptosis by Annexin V-FITC/PI double staining assay and up-regulate the expression of Bax and down-regulate the expression of PARP. Ultimately, we evaluated the effects of MF-P-5 on breast cancer via MDA-MB-231 cell xenograft in nude mice. The results of tumor volume and weight and immunohistochemistry revealed that MF-P-5 could significantly inhibit the growth of MDA-MB231 cells in vivo. Besides, the expression levels of E-cadherin significantly increased and MMP-2 decreased. The above results suggested that MF-P-5 could suppress the invasion of breast cancer cells in vivo. Furthermore, the expression level of Bcl-2 was prominently reduced which revealed that MF-P-5 stimulated the mitochondrial apoptosis pathway in vivo. As a result, MF5 could inhibit MDA-MB-231 and 4T1 cells proliferation, migration and tumor growth in vitro and MF-P-5 could suppress tumor growth in vivo which had laid a theoretical foundation for further clinical application.

Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,(1)H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25 kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy.

Background: Hypertension is a serious global public health issue. Blood pressure (BP) is still not effectively controlled in about 20 - 30% of hypertensive patients. Therefore, it is imperative to develop new treatments for hypertension. Veratrum alkaloids were once used for the clinical treatment of hypertension, the mechanism of which is still unclear. It was gradually phased out due to adverse reactions. Purpose: This study aimed to investigate the short-term and long-term hypotensive profiles of different compo-nents of Veratrum alkaloids in spontaneously hypertensive rats (SHRs) to unveil their mechanisms of action. Results: Total Veratrum alkaloid (V), component A (A), and veratramine (M) quickly decreased BP within 30 min of treatment, reduced renal and cardiovascular damage, and improved relevant biochemical indicators (nitric oxide [NO], endothelin-1 [ET-1], angiotensin II [Ang II)], noradrenaline [NE], etc) in SHRs to delay stroke occurrence. Thereinto, A exhibited excellent protective effects in cardiovascular disease. The metabolomic profiles of SHRs treated with V, A, and M were significantly different from those of SHRs treated with vehicle. Thirteen metabolites were identified as potential pharmacodynamic biomarkers. Through Kyoto Encyclopedia of Genes and Genomes analysis, V, A, and M-induced hypotension was mainly related to alterations in nicotinate and nicotinamide metabolism, GABAergic synapses, linoleic acid metabolism, ketone body synthesis and degradation, arginine and proline metabolism, and urea cycle, of which nicotinate and nicotinamide metabolism was the key metabolic pathway to relieve hypertension. Conclusion: This work shows that A is an effective and promising antihypertensive agent for hypertension treatment to reduce BP and hypertensive target organ damage, which is mainly mediated through modulating nicotinate and nicotinamide metabolism, RAS, and NO-ET homeostasis.

Abstract Ethanol is a principal ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol‐associated oxidative DNA damage in the central nervous system is well documented. Natural product may offer new options to protect the brain against ethanol‐induced neurotoxicity. The male flower of Eucommia ulmoides (EUF) Oliver has been extensively utilized as the tea, the healthy hot drink on the market. In this study, 19 constituents in the effective fraction of EUF were identified by ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). In the single‐cell gel electrophoresis assay, EUF was observed to ameliorate DNA damage in mouse cerebellum and cerebral cortex caused by acute ethanol administration, which was further confirmed by the morphological observation. The protective effects of EUF were associated with increasing total superoxide dismutase (T‐SOD) and glutathione peroxidase (GSH‐PX) activities, and a decrease in nitric oxide (NO), malondialdehyde (MDA), 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), and kelch‐like ECH‐associated protein‐1 (Keap1) levels. Molecular docking results demonstrated that compounds 4, 7, 9, and 16 from EUF have a strong affinity to the Keap1 Kelch domain to hinder the interaction of nuclear factor‐erythroid 2‐related factor 2 (Nrf2) with Keap1. These findings suggest that EUF is a potent inhibitor of ethanol‐induced brain injury possibly via the inhibition of oxidative stress.

药用植物学与生药学是药学、临床药学类专业的专业基础课程,是一门实践性、直观性、综合性很强的课程,且课程内容繁多松散、知识点掌握困难.根据多年的教学经验与积累,结合学生学习状态、自学能力和课程特点,围绕激发学生的学习兴趣和深化潜能,借助网络信息开展多形式、多元化的兴趣课堂的探索与实践,加强课程学习的实用性、综合性和创新性,培养出具有专业技能的药学人才.

Correction for 'Chemical compounds with a neuroprotective effect from the seeds of Celosia argentea L.' by Jinggong Guo et al., Food Funct., 2021, 12, 83-96, DOI: 10.1039/D0FO02033H.

野外实习是"药用植物学"的延续和深入,是培养学生理论联系实际、提高教学质量的一个重要环节.在国家大力发展中医药产业的新形势下,与时俱进,培养更优秀、更符合时代需求的中药人才,作者针对河南大学药学院"药用植物学"野外实习的现状及存在的问题提出了相应的改革措施.

Correction for 'Chemical compounds with a neuroprotective effect from the seeds of Celosia argentea L.' by Jinggong Guo et al., Food Funct., 2021, 12, 83-96, DOI: 10.1039/D0FO02033H.

Oxidative stress plays a central role in the common pathophysiology of neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. Antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Compounds derived from natural sources may offer the potential for new treatment options. Semen Celosiae is a traditional Chinese edible herbal medicine with a long history in China and exhibits wide-reaching biological activities such as hepatoprotective, anti-tumor, anti-diarrheal, anti-diabetic, anti-oxidant, etc. In this study, nine saponins and two phenylacetonitrile glycosides were isolated from Semen Celosiae and their structures were identified using ESI-MS and NMR techniques. Among them, compounds 1 and 2 have not been previously reported. The total concentrations of the five triterpenoid saponins and the two phenylacetonitrile glycosides were 3.348 mg g-1 and 0.187 mg g-1, respectively, suggesting that Semen Celosiae is a novel viable source of the two kinds of compounds. These compounds were observed to significantly attenuate t-BHP-induced neuronal damage by effectively enhancing cell viability and decreasing reactive oxygen species generation and cell apoptosis rate in NSC-34 cells. Furthermore, compounds 1 and 7 reduced the ratios of cleaved caspase-3: caspase-3 and cleaved caspase-7: caspase-7 and the level of cytochrome C, while they increased the levels of SOD1 and Beclin 1. These findings suggest that compounds 1-11 are potent inhibitors of neuron injury elicited by t-BHP, possibly via inhibition of oxidative stress and apoptosis, and activation of autophagy; therefore they may be valuable leads for future therapeutic development.

Veratrum plant contains a family of compounds called steroidal alkaloids which have been previously reported to cause DNA damage and blood pressure decrease in vivo. In this study, the antihypertensive effects and DNA damage in brain cells of 12 steroidal alkaloids separated from Veratrum plant were all evaluated to develop a relationship among chemical structure, antihypertensive activity and neurotoxicity by utilization of chemical principal component analysis (PCA) and hierarchical cluster analysis (HCA). Twelve steroidal alkaloids markedly reduced high blood pressure of hypertensive mice and also similarly induced varying degrees of DNA single-strand breaks in mouse cerebellum and cerebral cortex after oral administration. On the basis of the PCA and HCA results, it was suggested that the 3-carboxylic esters and benzene group play a core role in the DNA damage of brain cells, while more hydroxy groups in the A-ring and B-ring structure of jervine-type alkaloid led to stronger antihypertensive activity. The primary structure, activity and neurotoxicity relationship were discussed briefly.

"中药鉴定学"是中药学专业的必修专业课,也是一门实践理论紧密结合的课程,由于课程内容繁多松散、知识点掌握较为困难.根据多年的综合性院校中药学专业的教学经验与积累,结合学生学习状态、自学能力和中药鉴定学课程特点,借助网络信息技术,开展多种形式、多元化的"中药鉴定学"教学方法的探索与实践,以期为其他高等综合性院校开展"中药鉴定学"教学方法改革提供理论依据.

Ethanol is a principle ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol-associated oxidative DNA damage in the central nervous system is well documented. Natural source compounds may offer new options to protect the brain against ethanol-induced genotoxicity. Veratrum maackii Regel is a toxic rangeland plant linked to teratogenicity which is also used in traditional Chinese medicine as "Lilu" and is reported to contain a family of compounds called stilbenes that can have positive biological activity. In this study, nine stilbenes were isolated from the aerial parts of V. maackii Regel, and their structures were identified as cis-mulberroside A (1), resveratrol-4,3'- O-β-d-diglucopyranoside (2), mulberroside A (3), gentifolin K (4), resveratrol-3,5- O-β-d-diglucopyranoside (5), oxyresveratrol- 4'- O-β-d-glucopyranoside (6), oxyresveratrol-3- O-β-d-glucopyranoside (7), oxyresveratrol (8), and resveratrol (9) using ESI-MS and NMR techniques. The total concentration of extracted compounds 2-9 was 2.04 mg/g, suggesting that V. maackii Regel is a novel viable source of these compounds. In an in vivo comet assay, compounds 1-9 were observed to decrease DNA damage in mouse cerebellum and cerebral cortex caused by acute ethanol administration. Histological observation also revealed decreased brain injury in mice administered with compounds 1-9 after acute ethanol administration. The protective effects of compound 6 were associated with increasing T-SOD and GSH-PX activities and a decrease in NO and MDA concentrations. These findings suggest that these compounds are potent inhibitors of ethanol-induced brain injury possibly via the inhibition of oxidative stress and may be valuable leads for future therapeutic development.

Consequences of primary dsysmenorrhea (PD) can be severe. Increased prostaglandin production leads to uterine contraction and insufficient blood flow to the endometrium causing ischemia and pain symptoms. Protein tyrosine kinase/phosphatase activities contribute to the modulation of uterine contraction. In our previous study, we found the synthetic β-methoxyacrylates compound Fluacrypyrim (FAPM), significantly increased protein tyrosine phosphatases (PTPs) activity, resulting in dephosphorylation of tyrosine kinases. In the present study, we found that FAPM near completely inhibited prostaglandin F2α (PGF 2α )-, oxytocin-, acetylcholine-, and high K + -induced uterine contractions in rats in vitro, and decreased rat myometrial myosin light chain (MLC 20 ) phosphorylation induced by PGF 2α . A structure–activity relationship assay indicated that the β-methoxyacrylates structure of FAPM is crucial for the inhibition of PGF 2α -induced uterine contractions. FAPM caused a concentration-dependent parallel rightward shift of the concentration–response curve induced by oxytocin, dose-dependently reduced the number of abdominal constrictions and increased the latency time in PGF 2α - and acetic acid-induced writhing test in mice in vivo . Furthermore, FAPM considerably inhibited the development of Carr-induced rat paw edemas and thexylene-induced mouse ear edemas. Taken together, our results indicate that FAPM exerts antinociceptive and anti-inflammatory effects in vivo with considerable potential as a novel uterine relaxant.

A simple and sensitive high-performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry (Q-trap-MS) method was developed and validated for the determination of veratramine, the major bioactive and neurotoxic component in Veratrum nigrum L. Veratramine and the internal standard (IS) were separated with a Waters Symmetry C18 column and eluted with a gradient mobile phase system containing acetonitrile and 0.1% aqueous formic acid. The analysis was performed by using positive electrospray ionization mode with multiple reaction monitoring (MRM). Transition ions of m/z 410.2 → 295.2 for veratramine and m/z 426.1 → 113.8 for the IS were monitored. The method was validated with a good linearity in the range of 1-1000 ng/mL and lower limit of quantification of 1 ng/mL. The precision (CV) of intra- and inter-day ranged from 3.92 to 7.29%, while the accuracy (bias) intra- and inter-day were between -4.78 and 1.65%. The recovery, stability and matrix effect were within the acceptable ranges. Five metabolites of veratramine, including four hydroxylated and one sulfated metabolites, were tentatively identified using predictive MRM-information dependent acquisition-enhanced product ion mode (predictive MRM-IDA-EPI). The developed method was successfully applied to the pharmacokinetic and metabolic study of veratramine in mice after oral administration of veratramine. Copyright © 2016 John Wiley & Sons, Ltd.

The thromboxane (Tx) A2 pathway is a major contributor to the amplification of initial platelet activation and is therefore a key drug target. To identify potent small-molecule inhibitors of the thromboxane prostaglandin (TP) receptor, we screened a small steroidal saponin library using U46619-induced rat platelet aggregation assays. Timosaponin AIII (TAIII) was identified as a potent inhibitor of U46619-induced rat platelet aggregation and exhibited superior selectivity for the TP receptor versus other G protein-coupled receptors and a PKC activator. TAIII inhibited U46619-induced rat platelet aggregation independent of increases in cAMP and cGMP and the inhibition of TxA2 production. Both PKC and PLC activators restored TAIII-inhibited platelet aggregation, whereas TAIII did not inhibit platelet aggregation induced by co-activation of the G12/13 and Gz pathways. Furthermore, TAIII did not affect the platelet shape change or ROCK2 phosphorylation evoked by low-dose U46619. In vivo, TAIII prolonged tail bleeding time, reduced the mortality of animals with acute pulmonary thromboembolism and significantly reduced venous thrombus weight. Our study suggests that TAIII, by preferentially targeting Gq-mediated PLC/PKC signaling from the TP receptor, induces stronger in vitro antiplatelet activity and in vivo antithrombotic effects and may be an excellent candidate for the treatment of thrombotic disorders.

Veratramine (VAM) is the major lipid-soluble alkaloid existing in Veratrum nigrum L. that has been demonstrated to exert neurotoxic effects. To better understand the potential mechanism of neurotoxicity of VAM, VAM-induced DNA damage was measured in the cerebellum and cerebral cortex of mice after a 7-day repetitive oral dose by using single-cell gel electrophoresis (comet assay). A method based on high-performance liquid chromatography-electrospray ionization tandem mass spectrometry was developed for the determination of VAM and its in vivo and in vitro metabolites, to establish the potential correlation between metabolites and neurotoxicity. In vitro experiment was carried out using rat liver microsomes, whereas the in vivo study was conducted on rats at a single dose of 3 mg/kg. The results showed that VAM caused DNA damage in the cerebellum and cerebral cortex of mice in a dose-dependent manner. Phenyl mono-oxidation, sulfate conjugation and phenyl di-oxidation were proposed to be the main in vivo metabolic pathways of VAM, whereas the major in vitro metabolic pathways were phenyl mono-oxidation, hydroxylation and methylation. Phenyl-oxidation reaction was likely to be associated with reactive oxygen species production, leading to the DNA damage in the mouse brain.

To study the chemical constituents of Veratrum dahuricum (Turcz.) Loes. f., a new aurone glycoside named as (Z)-7, 4'-dimethoxy-6-hydroxyl-aurone-4-O-β-glucopyranoside was isolated from the 95% ethanol extracts of the rhizomes and roots of Veratrum dahuricum (Turcz.) Loes. f. by repeated column chromatography on silica gel and recrystallization. Its structure was established by extensive spectroscopic analyses, and its cytotoxicities against HepG-2, MCF7 and A549 cell lines were measured in vitro.