Sporoderm-broken spores of Ganoderma lucidum modulate hepatoblastoma malignancy by regulating RACK1-mediated autophagy and tumour immunity.

Hepatoblastoma (HB), a primary liver tumour, is notorious for its high metastatic potential and poor prognosis. Ganoderma lucidum, an edible mushroom species utilized in traditional Chinese medicine for addressing various tumour types, presents an intriguing avenue for HB treatment. However, the effectiveness of G. lucidum in managing HB and its underlying molecular mechanism necessitates further exploration. Standard in vitro assays were conducted to evaluate the impact of sporoderm-broken spores of G. lucidum (SBSGL) on the malignant characteristics of HB cells. The mechanism of SBSGL in treating HB and its tumour immunomodulatory effects were explored and validated by various experiments, including immunoprecipitation, Western blotting, mRFP-GFP-LC3 adenovirus transfection and co-localization analysis, as well as verified with in vivo experiments in this regard. The results showed that SBSGL effectively inhibited the malignant traits of HB cells and suppressed the O-GlcNAcylation of RACK1, thereby reducing its expression. In addition, SBSGL inhibited immune checkpoints and regulated cytokines. In conclusion, SBSGL had immunomodulatory effects and regulated the malignancy and autophagy of HB by regulating the O-GlcNAcylation of RACK1. These findings suggest that SBSGL holds promise as a potential anticancer drug for HB treatment.

The effect of herbal medicine in innate immunity to Candida albicans.

Candida albicans (C. albicans) is an opportunistic pathogenic fungus that often causes mucosal and systemic infections. Several pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and C-type lectin receptors (CLRs), have been implicated in the host recognition of C. albicans. These PRRs recognize the pathogen-associated molecular patterns (PAMPs) of C. albicans to activate innate immune cells, thereby rapidly inducing various inflammatory responses by activating intracellular signaling cascades. Herbal medicine and its active components deserve priority development due to their low toxicity and high antibacterial, antiviral and antifungal activities. This review discussed the activities of herbal compounds against C. albicans and their related mechanisms, especially their regulatory role on innate immune cells such as neutrophils, macrophages, and dendritic cells (DCs) implicated in C. albicans infections. Our work aims to find new therapeutic drugs and targets to prevent and treat diseases caused by C. albicans infection with the mechanisms by which this fungus interacts with the innate immune response.

Compound shougong powder inhibits the malignant phenotype of hepatocellular carcinoma cells by targeting the DNA damage repair pathway.

OBJECTIVES: Compound Shougong Powder (SGS), a traditional Chinese medicine formulation, has been used to treat cancer for many years with remarkable efficacy. However, the mechanisms underlying the therapeutic effect of SGS in Hepatocellular carcinoma (HCC) are not completely clear. METHODS: The survival and metastasis of HCC cells were examined by CCK-8 assay, EdU assay, Wound-healing and Transwell assay. The anti-tumour effect of SGS was studied using hoechst 33258 staining and flow cytometry. RNA sequencing was applied to detect the underlying mechanism. Comet DNA, qRT-PCR and WB experiments were performed for validation. In addition, HCC nude mouse model was constructed to detect SGS effect in vivo. KEY FINDINGS: SGS inhibited the proliferation, migration and invasion of HCC cells and induced apoptosis in vitro. In addition, SGS also suppressed tumour growth in a nude mouse model of HCC in a dose-dependent manner. RNA sequencing of the suitably treated HCC cells revealed significant changes in the expression levels of genes involved in the DNA damage repair pathway. The sequencing results were verified by Comet DNA, qRT-PCR, WB assays and molecular docking. CONCLUSIONS: Taken together, SGS inhibits the malignant phenotype of HCC cells by down-regulating DNA repair genes and consequently inducing DNA damage.

Protective effect of Huangpu Tongqiao capsule against Alzheimer's disease through inhibiting the apoptosis pathway mediated by endoplasmic reticulum stress in vitro and in vivo.

Objectives: Huangpu Tongqiao Capsule (HPTQC) is a traditional Chinese medicine (TCM) that has been used to treat Alzheimer's disease (AD). This study was to explore the pharmacological action and molecular mechanism of HPTQC in the treatment of AD. Methods: The possible targets of HTPQC were predicted by the molecular docking technique. Intraperitoneal injection of D-galactose and bilateral injection of Aß25-35 in hippocampus induced AD rat model. Morris water maze was used to observe learning and memory function. The primary hippocampal neurons were induced by Aß25-35. Moreover, the apoptosis rate of hippocampal nerve cells was detected through AnnexinV/PI double standard staining. The mRNA and protein levels of GRP78, CHOP, Caspase 12, Caspase 9, and Caspase 3 were detected by PCR and western blot. Results: The prediction results suggest that HPTQC may act on GRP78. HPTQC significantly improved the learning and memory function, and decreased neuronal apoptosis in vivo and in vitro. In addition, HPTQC could decrease the mRNA and protein expression levels of GRP78, CHOP, Caspase12, Caspase9, and Caspase3, and the effect trend was consistent with the specific inhibitor of GRP78. Conclusions: HPTQC has a neuroprotective effect against AD by inhibiting the apoptosis pathway mediated by endoplasmic reticulum stress.

Exploring the Absorption Mechanisms of Imidazolium-Based Ionic Liquids to Epigallocatechin Gallate.

Imidazolium-based ionic liquids are wildly used in natural product adsorption and purification. In this work, one typical polymeric ionic liquid (PIL) was synthesized by using L-proline as the anion, which exhibited excellent adsorption capacity toward tea polyphenol epigallocatechin gallate (EGCG). The adsorption conditions were optimized with the response surface method (RSM). Under the optimum conditions, the adsorption capacity of the PIL for EGCG can reach as high as 552 mg/g. Dynamics and isothermal research shows that the adsorption process of EGCG by the PIL particularly meets the quasi-second-order kinetic equation and monolayer adsorption mechanism. According to thermodynamic parameter analysis, the adsorption process is endothermic and spontaneous. The results of theoretical calculation by molecular docking also demonstrated the interaction mechanisms between EGCG and the ionic liquid. Considering the wide application of imidazolium-based ionic liquids in component adsorption and purification, the present study can not only be extended to other similar experimental mechanism validation, but also be representative for guiding the synthesis of PIL and optimization of adsorption conditions.

Research progress of matrine's anticancer activity and its molecular mechanism.

BACKGROUND: and ethnopharmacological relevance: Matrine (MT), a type of alkaloid extracted from the Sophora family of traditional Chinese medicine, has been documented to exert a variety of pharmacological effects, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrosis, and cardiovascular protection. Sophora flavescens Aiton is a traditional Chinese medicine that is bitter and cold. Additionally, it also exhibits the effects of clearing heat, eliminating dampness, expelling insects, and promoting urination. Malignant tumors are the most important medical issue and are also the second leading cause of death worldwide. Numerous natural substances have recently been revealed to have potent anticancer properties, and several have been used in clinical trials. AIMS OF THE STUDY: To summarize the antitumor effects and associated mechanisms of MT, we compiled this review by combining a huge body of relevant literature and our previous research. MATERIALS AND METHODS: As demonstrated, we grouped the pharmacological effects of MT via a PubMed search. Further, we described the mechanism and current pharmacological research on MT's antitumor activity. RESULTS: Additionally, extensive research has demonstrated that MT possesses superior antitumor properties, including accelerating cell apoptosis, inhibiting tumor cell growth and proliferation, inducing cell cycle arrest, inhibiting cancer metastasis and invasion, inhibiting angiogenesis, inducing autophagy, reversing multidrug resistance and inhibiting cell differentiation, thus indicating its significant potential for cancer treatment and prognosis. CONCLUSION: This article summarizes current advances in research on the anticancer properties of MT and its molecular mechanism, to provide references for future research.

Chrysophanol exerts neuroprotective effects via interfering with endoplasmic reticulum stress apoptotic pathways in cell and animal models of Alzheimer's disease.

OBJECTIVES: Chrysophanol (CHR), also well-known as Rhei radix et rhizome, is a crucial component in traditional Chinese medicine. It has been widely studied as a potential treatment for many diseases due to its anti-inflammatory effects. However, there are very few studies to establish the potential therapeutic effect of CHR in cell and animal models of Alzheimer's disease (AD). Therefore, we aim to investigate whether CHR could be used as a potential therapeutic approach to patients with AD and further disclose the underlying mechanism. Increasing studies have shown that endoplasmic reticulum (ER) calcium (Ca2+) homeostasis emerges as a central player in AD pathogenesis. Moreover, augmentation of ER stress (ERS) promotes neuronal apoptosis, and excessive oxidative stress is an inducer of ERS. Therefore, we believe that ERS-mediated apoptosis may be one of the causes of AD. METHODS: This study examined the neuroprotective effects of CHR on AD rats and AD cell models and explored its potential mechanism. KEY FINDINGS: CHR could reduce the damage of neurons. In AD cell models, CHR significantly inhibited Aß 25-35-induced neuronal damage, reduced the number of apoptotic cells and improved cell survival rate. Western blot showed that the expression of caspases 3, 9 and 12 was decreased after CHR treatment, and CHR also affected the ERS signalling pathway. In addition, the higher expression of pro-apoptotic proteins in the AD cell model was reduced after CHR treatment by inhibiting GRP78 signalling. Further studies have shown that overexpressed protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) inhibited the regulatory effect of CHR on PERK and weakened the neuroprotective effect of CHR on the AD cell model. CONCLUSIONS: This study revealed a novel mechanism through which CHR plays a neuroprotective role by regulating ERS when it comes to the therapy of AD.

A review of anti-tumour effects of ginsenoside in gastrointestinal cancer.

OBJECTIVES: Gastrointestinal cancer, one of the major causes of cancer-related deaths in the world, refers to malignant conditions of the gastrointestinal (GI) tract and other organs. Although conventional therapy has been successful to some extent in cancer treatment, drug resistance and cancer recurrence still limit the therapeutic efficacy. There is increasing evidence indicating that ginsenoside, as a kind of high nutritional value and widely used traditional Chinese medicine, could contribute to the promotion of treatment in GI cancer, which deserves further investigation. KEY FINDINGS: Based on previous studies, the possible mechanisms mainly include regulation of autophagy, apoptosis, proliferation, migration and angiogenesis. However, no studies recently have conducted a more in-depth review of the anti-cancer effects of ginsenoside in GI cancer. SUMMARY: Therefore, this review will summarise and analyse the latest developments in the anti-tumour effects of ginsenosides in GI cancer, thus may promote further research of the anti-tumour efficacy of ginsenoside.

Recent Research Progress in Natural Bioactive Constituents against Lipid Metabolic Diseases.

Lipid metabolic disorder refers to the dyslipidemia in the plasma. Abnormal working or lipid metabolism process leads to supernormal increase of one or multi kinds of lipids in plasma. It is a significant risk factor for many diseases and has become a serious danger to the mankind health. The clinical drugs adjusting lipid levels have a great variety in the market, side effects and adverse reactions. Meanwhile, many Chinese herbal medicines and natural medicines have the unnegligible role of regulating lipid metabolism, which become the research focus of medical workers in past decades. With advantages of fewer side effects, abundant resources and multi-target functions, terrestrial and marine bioactive constituents are proved as one of the important sources of the lead compounds in drug discovery and have been widely applied in the treatment and prevention of lipid metabolic diseases. In this paper, the recent advancements and current status of natural medicinal ingredients mainly based on lipid-lowering activities were reviewed in detail. Moreover, their bioactivity screening and important mechanisms in hyperlipemia progression were summarized and compared. It was also selectively introduced about related structural modification and new drug development on the basis of promising lead compounds. Finally, the current problems and possible prospects of natural constituents against lipid metabolism disorder in the future were discussed.

Application of step-wise gradient high-performance counter-current chromatography for rapid preparative separation and purification of diterpene components from Pseudolarix kaempferi Gordon.

In general, simultaneously separation and purification of components with a broad polarity range from traditional Chinese medicine (TCM) is a challenge by an ordinary high-speed counter-current chromatography (HSCCC) method. In this paper, we describes a rapid and efficient separation method of combining three-step gradient elution and two-step flow-rate gradient elution using high-performance counter-current chromatography (HPCCC) to separate 8 diterpene compounds simultaneously within 80 min in a single run from the alcohol extract of Pseudolarix kaempferi Gordon. This separation process produced 166 mg pseudolaric acid B O-ß-d-glucopyranoside (PABGly), 152 mg pseudolaric acid C (PAC), 8 mg deacetylpseudolaric acid A (deacetylPAA), 5 mg pseudolaric acid A O-ß-d-glucopyranoside (PAAGly), 484 mg pseudolaric acid B (PAB), 33 mg pseudolaric acid B methyl ester (PAB methyl ester), 10mg pseudolaric acid A (PAA) and 18 mg pseudolaric acid H (PAH) from 1.0 g crude sample with purities of 98.6%, 99.6%, 92.3%, 92.2%, 99.2%, 99.4%, 98.3%, 91.0%, respectively. Our study indicates that the suitable combination of step-wise gradient elution and flow-rate gradient elution using HPCCC is an effective strategy to separate complex components from natural products.

Preparative isolation and purification of three rotenoids and one isoflavone from the seeds of Millettia pachycarpa Benth by high-speed counter-current chromatography.

Both analytical and preparative high-speed counter-current chromatography (HSCCC) were used to isolate and separate chemical bioactive constituents from the seeds of Millettia pachycarpa Benth, a famous traditional Chinese medicine. Three rotenoids and one isoflavone were successfully purified for the first time by HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (HEMWat) (1:0.8:1:0.6, v/v/v/v). The separation parameters were first performed on the analytical HSCCC and optimized conditions were then scaled up to preparative HSCCC. The separation produced 160.2 mg tephrosin, 14.6 mg 4',5'-dimethoxy-6,6-dimethylpyranoisoflavone, 109.4 mg deguelin, 6.7 mg 6a,12a-dehydrodeguelin with respective purities of 95, 93, 95, 95%, in one single run from 400 mg crude extract of the seeds of M. pachycarpa Benth. The purity of the isolated compounds was analyzed by high-performance liquid chromatography (HPLC) and their structures were identified by electrospray ionization mass spectrometry (ESI-MS); (1)H nuclear magnetic resonance ((1)H NMR) and (13)C nuclear magnetic resonance ((13)C NMR) analysis. This paper is an excellent example of the role that CCC is playing in isolating active compounds for pre-clinical trials of new chemical entities, even when scaling up between centrifuges from different manufacturers.