Tissue distribution of metabolites in Cordyceps cicadae determined by DESI-MSI analysis.

In this paper, we establish an in situ visualization analysis method to image the spatial distribution of metabolites in different parts (sclerotium, coremium) and different microregions of Cordyceps cicadae (C. cicadae) to achieve the in situ visual characterization of tissues for a variety of metabolites such as nucleosides, amino acids, polysaccharides, organic acids, fatty acids, and so on. The study included LC-MS chemical composition identification, preparation of C. cicadae tissue sections, DEDI-MSI analysis, DESI combined with Q-TOF/MS to obtain high-resolution imaging of mass-to-charge ratio and space, imaging of C. cicadae in positive-negative ion mode with a spatial resolution of 100 µm, and localizing and identifying its chemical compositions based on its precise mass. A total of 62 compounds were identified; nucleosides were mainly distributed in the coremium, L-threonine and DL-isoleucine, and other essential amino acids; peptides were mainly distributed in the sclerotium of C. cicadae; and the rest of the amino acids did not have a clear pattern; sugars and sugar alcohols were mainly distributed in the coremium of C. cicadae; organic acids and fatty acids were distributed in the nucleus of C. cicadae more than in the sclerotium, and the mass spectrometry imaging method is established in the research. The mass spectrometry imaging method established in this study is simple and fast and can visualize and analyse the spatial distribution of metabolites of C. cicadae, which is of great significance in characterizing the metabolic network of C. cicadae, and provides support for the quality evaluation of C. cicadae and the study of the temporal and spatial metabolic network of chemical compounds.

Polypeptides from traditional Chinese medicine: Comprehensive review of perspective towards cancer management.

Cancer has always been a focus of global attention, and the difficulty of treatment and poor prognosis have always plagued humanity. Conventional chemotherapeutics and treatment with synthetic disciplines will cause adverse side effects and drug resistance. Therefore, searching for a safe, valid, and clinically effective drug is necessary. At present, some natural compounds have proved to have the potential to fight cancer. Polypeptides obtained from traditional Chinese medicine are good anti-cancer ingredients. The anticancer activity has been fully demonstrated in vivo and in vitro. However, most of the functional studies on traditional Chinese medicine polypeptides are at the stage of basic experimental research, and fewer of them have been applied to clinical trials. Hence, this review mainly discusses the chemical structure, extraction, separation and purification methods, the anti-cancer mechanism, and structure-activity relationships of traditional Chinese medicine polypeptides. It provides theoretical support for strengthening the rapid separation and purification and the overall efficacy and mechanism of action, as well as the industrialization and clinical application of traditional Chinese medicine polypeptides.

Synergistic mechanism of stir-baked curcumae radix with vinegar in dysmenorrhea rats based on UPLC-Q-TOF/MS metabolomics.

Curcumae Radix (i.e. Huangsiyujin: HSYJ), a well-known traditional Chinese medicine (TCM), has been widely used in clinical practice for many years to treat depression and primary dysmenorrhea. Modern pharmacological researches have demonstrated its anti-inflammatory, antidepressant, and dysmenorrhea relief effects. According to the processing theory of TCM, it is believed that stir-baked HSYJ with vinegar may enhance the ability to disperse stagnant hepatoqi and alleviate pain. However, whether the vinegar concoction of HSYJ can enhance the therapeutic effect on the Qi stagnation due to liver depression (LDQS) type of dysmenorrhea and what its mechanism has not been well explained. Based on the processing drugs theory of "stir-baked with vinegar into liver", a metabolomic approach was used to investigate the therapeutic effect and mechanism of stir-baked HSYJ with vinegar to enhance the treatment of dysmenorrhea in rats. By establishing a rat model of dysmenorrhea of the "LDQS" type, observation of hemorheology, uterine pathological sections, COX-2 and OTR protein expression and other indicators; analysis of urinary metabolic changes in rats by UPLC-Q-TOF-MS technique, to compare the differential biomarkers and metabolic pathways in the treatment of dysmenorrhea due to "liver stagnation and qi stagnation" before and after stir-baked HSYJ with vinegar. Stir-baked HSYJ with vinegar significantly inhibited the writhing response of rats, improved hemorheology, repaired damaged diseased uterus and inhibited high expression of COX-2 and OTR proteins in uterus; 68 differential metabolites were screened from the urine of rats, compared with the raw HSYJ, the levels of 14 metabolites were significantly changed in stir-baked HSYJ with vinegar, involving the pathways of phenylalanine, tyrosine and tryptophan metabolism, cysteine and methionine metabolism, aspartate and glutamate metabolism. The potentiating effect of stir-baked HSYJ with vinegar may be related to the regulation of multiple amino acid metabolic pathways.

US of thyroid nodules: can AI-assisted diagnostic system compete with fine needle aspiration?

OBJECTIVES: Artificial intelligence (AI) systems can diagnose thyroid nodules with similar or better performance than radiologists. Little is known about how this performance compares with that achieved through fine needle aspiration (FNA). This study aims to compare the diagnostic yields of FNA cytopathology alone and combined with BRAFV600E mutation analysis and an AI diagnostic system. METHODS: The ultrasound images of 637 thyroid nodules were collected in three hospitals. The diagnostic efficacies of an AI diagnostic system, FNA-based cytopathology, and BRAFV600E mutation analysis were evaluated in terms of sensitivity, specificity, accuracy, and the κ coefficient with respect to the gold standard, defined by postsurgical pathology and consistent benign outcomes from two combined FNA and mutation analysis examinations performed with a half-year interval. RESULTS: The malignancy threshold for the AI system was selected according to the Youden index from a retrospective cohort of 346 nodules and then applied to a prospective cohort of 291 nodules. The combination of FNA cytopathology according to the Bethesda criteria and BRAFV600E mutation analysis showed no significant difference from the AI system in terms of accuracy for either cohort in our multicenter study. In addition, for 45 included indeterminate Bethesda category III and IV nodules, the accuracy, sensitivity, and specificity of the AI system were 84.44%, 95.45%, and 73.91%, respectively. CONCLUSIONS: The AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with BRAFV600E mutation analysis. Given its advantages in terms of operability, time efficiency, non-invasiveness, and the wide availability of ultrasonography, it provides a new alternative for thyroid nodule diagnosis. CLINICAL RELEVANCE STATEMENT: Thyroid ultrasonic artificial intelligence shows statistically equivalent performance for thyroid nodule diagnosis to FNA cytopathology combined with BRAFV600E mutation analysis. It can be widely applied in hospitals and clinics to assist radiologists in thyroid nodule screening and is expected to reduce the need for relatively invasive FNA biopsies. KEY POINTS: • In a retrospective cohort of 346 nodules, the evaluated artificial intelligence (AI) system did not significantly differ from fine needle aspiration (FNA) cytopathology alone and combined with gene mutation analysis in accuracy. • In a prospective multicenter cohort of 291 nodules, the accuracy of the AI diagnostic system was not significantly different from that of FNA cytopathology either alone or combined with gene mutation analysis. • For 45 indeterminate Bethesda category III and IV nodules, the AI system did not perform significantly differently from BRAFV600E mutation analysis.

Anticancer perspective of 6-shogaol: anticancer properties, mechanism of action, synergism and delivery system.

Cancer is a malignant disease that has plagued human beings all the time, but the treatment effect of commonly used anticancer drugs in clinical practice is not ideal by reason of their drug tolerance and Strong adverse reactions to patients. Therefore, it is imperative to find effective and low-toxic anticancer drugs. Many research works have shown that natural products in Chinese herbal medicine have great anticancer potential, such as 6-shogaol, a monomer composition obtained from Chinese herbal ginger, which has been confirmed by numerous in vitro or vivo studies to be an excellent anti-cancer active substance. In addition, most notably, 6-shogaol has different selectivity for normal and cancer cells during treatment, which makes it valuable for further research and clinical development. Therefore, this review focus on the anti-cancer attributes, the mechanism and the regulation of related signaling pathways of 6-shogaol. In addition, its synergy with commonly used anticancer drugs, potential drug delivery systems and prospects for future research are discussed. This is the first review to comprehensively summarize the anti-cancer mechanism of 6-shogaol, hoping to provide a theoretical basis and guiding significance for future anti-cancer research and clinical development of 6-shogaol.

Research progress on the treatment of epilepsy with traditional Chinese medicine.

BACKGROUND: Traditional Chinese Medicine (TCM) system is a medical system that has been expanding for thousands of years that was formed by the extensive clinical practice experience of many physicians and the accumulation of personal medication habits in China. In TCM, there is a history of long-term medication for epilepsy, the main treatment for epilepsy is TCM drugs and its prescription, supplemented by TCM modalities such as acupuncture therapy, moxibustion therapy, tuina, emotion adjustment therapy, etc. PURPOSE: With the modernization of TCM, the active ingredients and molecular mechanisms of TCM for epilepsy treatment have been gradually revealed. This review aimed to comprehensively summarize the TCM treatment of epilepsy, focusing on the current TCM drugs and some TCM formulae for the treatment of epilepsy, and to discuss the research progress of TCM for the treatment of epilepsy, and to provide a reference to develop future related studies in this field. MATERIALS AND METHODS: The mechanism of action of antiepileptic drugs (AEDs) was interpreted from different perspectives by searching online databases and querying various materials identify drugs used in both modern medicine and TCM systems for the treatment of epilepsy. We collected all relevant TCM for epilepsy literature published in the last 30 years up to December 2022 from electronic databases such as PubMed, CNKI and Web of Science, and statistically analyzed the literature for the following keyword information. The search terms comprise the keywords "TCM", "phytochemistry", "pharmacological activity", "epilepsy" and "traditional application" as a combination. Scientific plant names were provided by "The Plant List" (www.theplantlist.org). RESULTS: Epilepsy is a complex and serious disease of the brain and nervous system. At present, the treatment of epilepsy in modern medicine is mainly surgery and chemotherapy, but there are many serious side effects. By summarizing the treatment of epilepsy in TCM, it is found that there are various methods to treat epilepsy in TCM, mainly TCM drugs and its formulae. Many TCM drugs have antiepileptic effects. Now found that the main effective TCM drugs for the treatment of epilepsy are Curcumae Longae Rhizoma, Scorpio, Acori Tatarinowii Rhizoma, Uncariae Ramulus Cum Uncis and Ganoderma, etc. And the main compounds that play a role in the treatment of epilepsy are curcumin, gastrodin, ligustrazine, baicalin and rhynchophylline, etc. These TCM drugs have played an important role in the treatment of epilepsy in TCM clinic. However, the chemically active components of these TCM drugs are diverse and their mechanisms of action are complex, which are not fully understood and need to be further explored. CONCLUSIONS: TCM treats epilepsy in a variety of ways, and with the discovery of a variety of potential bioactive substances for treatment of epilepsy. With the new progress in the research of other TCM treatment methods for epilepsy, TCM will have greater potential in the clinical application of epilepsy.

Polysaccharides from Chinese materia medica: Perspective towards cancer management.

Cancer has always been a focus of global attention, and the difficulty of treatment and poor prognosis have always plagued humanity. Conventional chemotherapeutics and treatment with synthetic disciplines will cause adverse side effects and drug resistance. Therefore, searching for a safe, valid, and clinically effective drug is necessary. At present, some natural compounds have proved to have the potential to fight cancer. Polysaccharides obtained from Chinese materia medica are good anti-cancer ingredients. Polysaccharides are macromolecular compounds of equal or distinct monosaccharides with an α- or ß-glycosidic bonds. The anti-cancer activity has been fully demonstrated in vivo and in vitro. However, Chinese materia medica polysaccharides are only used as adjuvant therapy for cancer-related diseases. Hence, this review mainly discusses the chemical composition, biological activity, absorption in vivo, and clinical application of Chinese materia medica polysaccharides. Also, we discussed the anti-cancer mechanism. We also discussed the current research's limitations on treating cancer with Chinese materia medica polysaccharides and insights into future research.

Ligustri Lucidi Fructus, a traditional Chinese Medicine: Comprehensive review of botany, traditional uses, chemical composition, pharmacology, and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligustri Lucidi Fructus (LLF) is one of the usual Chinese herbs that has long been used with high therapeutic and condition value. LLF is used for the treatment of dizziness and tinnitus, soreness and weakness of the waist and knees, premature greying of the hair, the darkness of the eyes, internal heat and thirst, bone steam and hot flashes and other symptoms. AIM OF THE STUDY: This review reviews botany, traditional uses, processing, phytochemistry, quality control, pharmacology, toxicity and pharmacokinetics to better understand its therapeutic potential. MATERIALS AND METHODS: The literature on LLF was obtained from Google Scholar and Baidu Scholar, PubMed, ScienceDirect, SciFinder, Web of Science, China National Knowledge Infrastructure (CNKI), WAN FANG DATA and libraries. Some local books, official websites, PhD or MS's dissertations were also included. Phytochemical constituents' structures were drawn by ChemDraw software. RESULTS: So far, Multiple chemical components were isolated and identified from LLF, mainly including terpenoids and flavonoids. Modern studies have shown that LLF extracts and compounds have a wide range of pharmacological effects, including antitumor, liver protection, blood glucose, lipid-lowering, immune regulation, and other aspects. CONCLUSIONS: LLF occupies an important position in the traditional medical system. It is cost-effective and is a significant plant with therapeutic applications in modern medicine. However, further in-depth studies are needed to determine the medical use of this plant and its chemical composition, pharmacological activity, quality control, toxicity and pharmacokinetics.

Effect of Wuzi Yanzong prescription on oligoasthenozoospermia rats based on UPLC-Q-TOF-MS metabolomics.

CONTEXT: Wuzi Yanzong Prescription (WYP) has long been used to treat male infertility, with convincing clinical evidence. However, its mechanism of action is not clear. OBJECTIVE: WYP chemical components were quantified by HPLC, and the effect on oligoasthenozoospermia rats was explored based on UPLC-Q-TOF-MS metabonomics technology. MATERIALS AND METHODS: The solution was extracted by alcohol and water; the content of eight components in the extracting solution was determined by HPLC. Twenty-four Sprague-Dawley rats were randomly divided into control (CG), model (MG) and administration (PG) groups. Oligoasthenozoospermia was induced for 30 days in all, but the CG with daily oral doses of 20 mg/kg Tripterysium glycosides (TG). PG was given daily oral doses of WYP solution (1.08 g/kg), CG and MG received the same volume of distilled water, all administered for 30 days. After the last administration, the serum samples were collected and detected by UPLC-Q-TOF-MS. RESULTS: An HPLC method for simultaneous determination of chlorogenic acid (0.081%), ellagic acid (0.021%), hyperoside (0.032%), verbascoside (0.011%), isoquercitrin (0.041%), astragalin (0.026%), kaempferol (0.009%) and schisandrin (0.014%) was established. Moreover, the 74 potential biomarkers and eight metabolic pathways related to oligoasthenozoospermia were identified by multivariate analysis and metabolite profiling. WYP can regulate 36 markers, mainly involving amino acid metabolism, lipid metabolism and nucleotide metabolism. DISCUSSION AND CONCLUSIONS: This is a simple and accurate method for quality control of WYP. It further enriches the potential mechanism of WYP in the treatment of oligoasthenozoospermia. It can provide a theoretical basis for the rational application of WYP.

Molecular characterization of a profilin gene from a parasitic ciliate Cryptocaryon irritans.

Profilin, known as one of the core actin-binding proteins, is an integral part of actin-based cytoskeleton involved in cell motility, cytokinesis, neuronal differentiation, and synaptic plasticity. In this study, a putative profilin gene designated as CiProfilin (GenBank accession number: JX987286) was screened out from a cDNA library of Cryptocaryon irritans trophonts. The full-length cDNA of CiProfilin gene is 582 bp, containing an open reading frame (ORF) of 471 bp, which encodes a polypeptide consisting of 156 amino acids with a predicted molecular weight of 17.3 kDa. Quantification of CiProfilin mRNA expression by real-time PCR suggested that CiProfilin was expressed in all stages of C. irritans life cycle with a significantly higher level in trophonts. Five non-universal codons (TAAs) coding glutamines (Gln) were found in the ORF and mutated to CAAs (universal codons for Gln) by site-directed mutagenesis. Then the modified ORF was inserted into the plasmid pGEX-4T-1, the recombinant plasmid was subsequently transformed into Escherichia coli. The bacteria were subsequently induced to express the recombinant CiProfilin protein fused with glutathione S transferase (G-rCiProfilin), which was then purified with glutathione sepharose 4B and thrombin cleavage. The molecular weight and the antigenicity of rCiProfilin were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. The native CiProfilin was found abundant in the peripheral area beneath the cell membrane and around the cytostomes of theronts, suggesting its vital roles in food uptake, stomatogenesis, and parasitic invasion. Co-precipitation assay also revealed the activity of rCiProfilin in actin binding. This study will help further elucidate the specific roles of CiProfilin on the growth of C. irritans and the preliminary mechanism of its invasion to hosts.

Curcumae Radix: a review of its botany, traditional uses, phytochemistry, pharmacology and toxicology.

OBJECTIVES: Curcumae Radix, the medicinal part is radix, commonly called as Yujin (Chinese:), is a widely used traditional Chinese medicine for its high medicinal value and health benefits. Curcumae Radix has been used to treat conditions such as syndrome of heat disease and unconsciousness, epilepsy and internal stagnation of phlegm, qi stagnation and blood stasis, dysmenorrhoea, jaundice, cholelithiasis caused by dampness heat of liver and gallbladder. This review aims to summarize the botany, traditional usages, processing, phytochemistry, quality control, pharmacology and toxicology of Curcumae Radix to better understand its therapeutic potential. KEY FINDINGS: So far, a variety of chemical constituents have been isolated and identified from Curcumae Radix, mainly including volatile oil and diphenylheptanes. Modern research shows that the extracts and compounds from Curcumae Radix possess wide-ranging pharmacological effects, including anti-tumour, hepatoprotective, anti-inflammatory and analgesic, anti-thrombosis, as well as effects on the nervous system and others. SUMMARY: Curcumae Radix holds an important position in traditional system of medicine. It is cost-effective and an important plant with curative application in contemporary medicine. However, further in-depth studies are also needed to determine the medical uses of this plant and its chemical constituents, pharmacological activity, quality control and toxicology.

Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures.

Curcumin is a natural compound with great potential for disease treatment. A large number of studies have proved that curcumin has a variety of biological activities, among which anti-inflammatory effect is a significant feature of it. Inflammation is a complex and pervasive physiological and pathological process. The physiological and pathological mechanisms of inflammatory bowel disease, psoriasis, atherosclerosis, COVID-19 and other research focus diseases are not clear yet, and they are considered to be related to inflammation. The anti-inflammatory effect of curcumin can effectively improve the symptoms of these diseases and is expected to be a candidate drug for the treatment of related diseases. This paper mainly reviews the anti-inflammatory effect of curcumin, the inflammatory pathological mechanism of related diseases, the regulatory effect of curcumin on these, and the latest research results on the improvement of curcumin pharmacokinetics. It is beneficial to the further study of curcumin and provides new ideas and insights for the development of curcumin anti-inflammatory preparations.

Zingiberis Rhizoma Recens: A Review of Its Traditional Uses, Phytochemistry, Pharmacology, and Toxicology.

Zingiberis Rhizoma Recens (ZRR, the fresh rhizoma of Zingiber officinale Roscoe) is a widely used traditional Chinese medicine (TCM). It is also a traditional spice, widely used around the world. The present paper reviews advances in research relating to the botany, ethnopharmacology, phytochemistry, pharmacology, and toxicology of Zingiberis Rhizoma Recens. In addition, this review also discusses some significant issues and the potential direction of future research on Zingiberis Rhizoma Recens. More than 100 chemical compounds have been isolated from Zingiberis Rhizoma Recens, including gingerols, essential oils, diarylheptanoids, and other compounds. Modern studies have confirmed that Zingiberis Rhizoma Recens has pharmacological effects on the nervous system and cardiovascular and cerebrovascular systems, as well as antiemetic, antibacterial, antitumor, anti-inflammatory, and antioxidant effects. However, the modern studies of Zingiberis Rhizoma Recens are still not complete and more bioactive components and potential pharmacological effects need to be explored in the future. There is no unified standard to evaluate the quality and clinical efficacy of Zingiberis Rhizoma Recens. Therefore, we should establish reasonable, accurate, and reliable quality control standards to make better use of Zingiberis Rhizoma Recens.

Study on Quality Standards and Hepatoprotective Effect of Curcuma phaeocaulis Radix.

Curcuma phaeocaulis Radix (Lüsiyujin) is a mainstream variety of Curcumae Radix cultivated in Sichuan for more than 900 years, but its broader utility is limited by a lack of quality control and pharmacodynamic research. We used the Chinese Pharmacopoeia, 2015 edition, to guide the determination of germacrone and furanodienone content in extracts. We established an animal model of Qi stagnation and blood stasis in a clinical context. Pathological changes in liver function indexes were evaluated to investigate the hepatoprotective effect of Lüsiyujin. In 20 extraction batches of Lüsiyujin, ethanol extracts yielded 9.22%-15.01%, average 12.03%. The germacrone content was 0.003%-0.011% (average 0.0069%), and the furanodienone content was 0.090%-0.478% (average 0.201%). Compared with the control group, the model rats exhibited functional liver damage. Serum markers of liver function varied after treatment with Lüsiyujin, but significant effects were observed with alanine aminotransferase and total bile acid. This study demonstrates a simple method of quality control for Lüsiyujin. The study also demonstrated that Lüsiyujin inhibits hepatocyte damage and regulates the excretion and secretion of hepatic bile. Our findings provide a theoretical basis for the formulation of quality standards, clinical application, and resource development for the utilisation of Lüsiyujin.

Radiofrequency Ablation of Parathyroid Glands to Treat a Patient With Hypercalcemia Caused by a Novel Inactivating Mutation in CaSR.

Objective: We identified a novel inactivating mutation in the calcium-sensing receptor (CaSR) gene in a patient with refractory hypocalciuric hypercalcemia and analyzed its function. The effectiveness of radiofrequency ablation of the parathyroid glands to treat hypercalcemia caused by this mutation was explored. Methods: Clinical data of patients before and after radiofrequency ablation were retrospectively analyzed. The CaSR mutation (D99N) found in the patient was studied in cell lines. HEK-293 cells were transfected with plasmids containing wild-type (WT) or mutant CaSR genes (D99N and W718X). Expression levels of the respective CaSR proteins were measured, and their functions were assessed by examining the effect of NPS R-568 (a CaSR agonist) on intracellular Ca2+ oscillations and that of exogenous parathyroid hormone (PTH) on intracellular cyclic adenosine monophosphate (cAMP) levels. Results: The effectiveness of pharmacological treatment was poor, whereas radiofrequency ablation of the parathyroid glands resulted in controlled blood calcium and PTH levels in the patient. In cell lines, upon NPS R-568 administration, the amplitude of intracellular Ca2+ oscillations in the D99N group was lower than that in the WT group and higher than that in the W718X group. Upon administration of PTH, intracellular cAMP levels in the D99N group were higher than those in the WT group and lower than those in the W718X group. Conclusion: The homozygous mutation D99N reduced CaSR activity and caused more severe hypocalciuric hypercalcemia. For patients with this type of hypercalcemia and poor response to pharmacological treatments, radiofrequency ablation of the parathyroid glands may be a suitable treatment option.

Different Processed Products of Curcumae Radix Regulate Pain-Related Substances in a Rat Model of Qi Stagnation and Blood Stasis.

BACKGROUND: Curcumae blood Radix (Yujin) has been widely used to treat Qi stagnation and stasis in TCM. According to the Chinese Pharmacopoeia, the tuberous roots of Curcuma longed L. (i.e., Huangsiyujin, HSYJ) is one of the major species of Yujin. According to the processing theory of TCM, stir-frying HSYJ with vinegar might strengthen the effect of dispersing stagnated hepatoqi to relieve pain, and stir-frying HSYJ with wine might strengthen the effect of promoting blood circulation in order to remove blood stasis. However, the mechanism for the enhancement of clinical efficacy by processing is unclear. AIM/HYPOTHESIS: This study was aimed at evaluating the effect of different processed products of HSYJ on chemical constituents and pain-related substances to explore underlying mechanisms of HSYJ in treating pain caused by Qi stagnation and blood stasis. METHODS: The effects of different processing methods on the paste yield of water decoction were analyzed, and the content of the main constituents were detected by HPLC. A rat model of Qi stagnation and blood stasis was established by tail clamp stimulation combined with subcutaneous adrenaline injection. After treatment and intervention with HSYJ and its processed products, ß-endorphin (ß-EP) and 5-hydroxytryptamine (5-HT) were measured by ELISA, and the expression of c-fos was evaluated by immunohistochemistry. RESULTS: After stir-frying with vinegar or wine, the extract yield and curcumin content increased. Compared with model group, raw HSYJ could significantly improve the abnormality of 5-HT in plasma (P < 0.05) and ß-EP in brain (P < 0.01). Stir-frying HSYJ with vinegar or wine could significantly improve the abnormality of 5-HT in plasma, ß-EP in brain, and the expression of c-fos (P < 0.01). Stir-frying HSYJ with vinegar could also significantly increase the level of ß-EP in plasma (P < 0.05). CONCLUSION: These results showed that different processing methods have certain effects on the chemical constituents of HSYJ, mainly in increasing the decoction rate and curcumin content. HSYJ and its processed products can reduce 5-HT levels, increase ß-EP levels, and inhibit the expression of c-fos in model rats. The effects of stir-frying HSYJ with vinegar on ß-EP levels in plasma was superior to others.

Limonin: A Review of Its Pharmacology, Toxicity, and Pharmacokinetics.

Limonin is a natural tetracyclic triterpenoid compound, which widely exists in Euodia rutaecarpa (Juss.) Benth., Phellodendron chinense Schneid., and Coptis chinensis Franch. Its extensive pharmacological effects have attracted considerable attention in recent years. However, there is no systematic review focusing on the pharmacology, toxicity, and pharmacokinetics of limonin. Therefore, this review aimed to provide the latest information on the pharmacology, toxicity, and pharmacokinetics of limonin, exploring the therapeutic potential of this compound and looking for ways to improve efficacy and bioavailability. Limonin has a wide spectrum of pharmacological effects, including anti-cancer, anti-inflammatory and analgesic, anti-bacterial and anti-virus, anti-oxidation, liver protection properties. However, limonin has also been shown to lead to hepatotoxicity, renal toxicity, and genetic damage. Moreover, limonin also has complex impacts on hepatic metabolic enzyme. Pharmacokinetic studies have demonstrated that limonin has poor bioavailability, and the reduction, hydrolysis, and methylation are the main metabolic pathways of limonin. We also found that the position and group of the substituents of limonin are key in affecting pharmacological activity and bioavailability. However, some issues still exist, such as the mechanism of antioxidant activity of limonin not being clear. In addition, there are few studies on the toxicity mechanism of limonin, and the effects of limonin concentration on pharmacological effects and toxicity are not clear, and no researchers have reported any ways in which to reduce the toxicity of limonin. Therefore, future research directions include the mechanism of antioxidant activity of limonin, how the concentration of limonin affects pharmacological effects and toxicity, finding ways to reduce the toxicity of limonin, and structural modification of limonin-one of the key methods necessary to enhance pharmacological activity and bioavailability.

Cinnamomum cassia Presl: A Review of Its Traditional Uses, Phytochemistry, Pharmacology and Toxicology.

Cinnamomum cassia Presl is a tropical aromatic evergreen tree of the Lauraceae family, commonly used in traditional Chinese medicine. It is also a traditional spice, widely used around the world. This paper summarizes the achievements of modern research on C. cassia, including the traditional uses, phytochemistry, pharmacology and toxicology. In addition, this review also discusses some significant issues and the potential direction of future C. cassia research. More than 160 chemicals have been separated and identified from C. cassia. The main constituents of C. cassia are terpenoids, phenylpropanoids, glycosides, etc. Modern studies have confirmed that C. cassia has a wide range of pharmacological effects, including antitumour, anti-inflammatory and analgesic, anti-diabetic and anti-obesity, antibacterial and antiviral, cardiovascular protective, cytoprotective, neuroprotective, immunoregulatory effects, anti-tyrosinase activity and other effects. However, the modern studies of C. cassia are still not complete and more in-depth investigations need to be conducted in alimentotherapy, health product, toxicity and side effects, and more bioactive components and potential pharmacological effects need to be explored in the future.

Agkistrodon ameliorates pain response and prevents cartilage degradation in monosodium iodoacetate-induced osteoarthritic rats by inhibiting chondrocyte hypertrophy and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA), characterized by joint pain and cartilage degradation, is the most common form of joint disease worldwide but with no satisfactory therapy available. The ethanol extract of Agkistrodon acutus (EAA) has been widely used as a traditional Chinese medicine (TCM) for the treatment of arthralgia and inflammatory diseases, but there is no report regarding its efficacy on OA to date. Here, we determined the effects of EAA on the pain behavior and cartilage degradation in vivo and clarified its target genes and proteins associated with chondrocyte hypertrophy and apoptosis in vitro. MATERIALS AND METHODS: In vivo OA model was established by intra-articular injection (1.5 mg) of monosodium iodoacetate (MIA) into rats and weekly treated by intra-articular administration of EAA at a dose range from 0.3 to 0.9 g/kg for four weeks. The pain behavior parameters, thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were tested before and after the treatment. Then histopathologic, immunohistochemical and TUNEL analyses of the articular cartilage were conducted, followed by Mankin's scoring. In vitro, the effects of EAA on chondrocytes were evaluated via assays of cell viability, immunofluorescence, real time PCR, and Western blot. UPLC-MS was applied to determine the chemical composition of EAA. RESULTS: The animal data showed that EEA not only attenuated the pain hypersensitivity but also blocked the cartilage degeneration by improving chondrocyte survival and suppressing chondrocyte apoptosis at a dose-dependent manner in OA rats. Furthermore, EAA remarkably restored the abnormal expression of collagen type II (Col2) and matrix metalloproteinase-13 (MMP13) in cartilage of OA rats. The cellular data showed that EAA significantly increased the cell viability of chondrocytes against OA-like damage and restored the abnormal expressions of Col2 and MMP13 in damaged chondrocytes. The molecular data showed that EAA significantly restored the abnormal mRNA expressions of Col2, Col10, MMP2 and MMP13 as well as the abnormal protein expressions of MMP13, PARP (total and cleaved) in chondrocytes under pathological condition. UPLC-MS analysis showed the known main components of EAA, including amino acides (glycine, L-aspartic acid, L-glutamic acid, and L-hydroxyproline), nucleoside (uridine), purines (xanthine and hypoxanthine), and pyrimidine (uracil). CONCLUSIONS: Our data demonstrate that EAA exerts antinociceptive and chondroprotective effects on OA through suppressing chondrocyte hypertrophy and apoptosis with restoration of the molecular expressions of anabolism and catabolism in chondrocytes. It provides a promising TCM candidate of novel agent for OA therapy.

Intra-Articular Injection of Fructus Ligustri Lucidi Extract Attenuates Pain Behavior and Cartilage Degeneration in Mono-Iodoacetate Induced Osteoarthritic Rats.

Fructus Ligustri Lucidi (FLL) has been widely used as a traditional Chinese medicine (TCM) for treating soreness and weakness of waist and knees. It has potential for treating OA owing to its kidney-tonifying activity with bone-strengthening effects, but there is so far no report of its anti-OA effect. This study established a rat OA model by intra-articular (IA) injection of mono-iodoacetate (1.5 mg) and weekly treated by IA administration of FLL at 100 µg/mL for 4 weeks. Thermal withdrawal latency, mechanical withdrawal threshold, and spontaneous activity were tested for evaluation of pain behavior, and histopathological (HE, SO, and ABH staining) and immunohistochemical (Col2, Col10, and MMP13) analyses were conducted for observation of cartilage degradation. In vitro effect of FLL on chondrocytes was evaluated by MTT assay and qPCR analysis. Moreover, HPLC analysis was performed to determine its chemoprofile. The pain behavioral data showed that FLL attenuated joint pain hypersensitivity by increasing thresholds of mechanical allodynia and thermal hyperalgesia as well as spontaneous activity. The histopathological result showed that FLL reversed OA cartilage degradation by protecting chondrocytes and extracellular matrix in cartilage, and the immunohistochemical analysis revealed its molecular actions on protein expressions of MMP13, Col2, and Col10 in cartilage. The MTT assay showed its proliferative effects on chondrocytes, and qPCR assay clarified its mechanism associated with gene expressions of Mmp13, Col2, Col10, Adamts5, Aggrecan, and Runx2 in TNF-α treated chondrocytes. Our results revealed an anti-OA effect of FLL on pain behavior and cartilage degradation in OA rats and clarified a molecular mechanism in association with the suppression of chondrocyte hypertrophy and catabolism. IA FLL can be regarded as novel and promising option for OA therapy.