This article systematically analyzed the historical evolution of the name， origin， harvesting and others of Longan Arillus by referring to the ancient and modern literature， in order to provide a foundation for developing famous classical formulas containing this herb. After textual research， it indicated that Longan Arillus was first recorded under the name of longan in Shennong Bencaojing of the Han dynasty. During the Ming and Qing dynasties， Longan Arillus gradually replaced longan as the standard name recorded in the materia medica， with additional aliases including Yizhi， Lizhinu and Yuanyan. The source of Longan Arillus used in the past dynasties was the arillus of the Sapindaceae plant Dimocarpus longan. The production regions recorded in the past dynasties were mainly Fujian， Guangdong， Guangxi， Hainan， Sichuan and others. Since the Qing dynasty， Longan Arillus produced in Fujian， Guangdong and Guangxi have been regarded as the finest and authentic varieties， with Fujian， Guangxi， and Guangdong remaining the primary authentic production areas today. In ancient times， the fruits were primarily harvested in August of the lunar calendar. However， modern longan cultivation typically involves harvesting ripe fruits during summer and autumn. Post-harvest processing involves removing moisture through sun-drying or baking before drying for medicinal use. Throughout history， processing methods have primarily focused on raw product， though techniques such as wine soaking and powdering have also been employed. Since modern times， it has been concluded that its quality is the best one with thick flesh， sweet taste， brownish-yellow color and tender texture. Longan Arillus possesses a sweet and warm nature， entering the heart and spleen meridians. Its primary functions are tonifying the heart and spleen， nourishing the blood and calming the spirit， which is consistent in ancient and modern times. Based on the textual research， it is suggested to use the arillus of D. longan when developing the famous classical formulas containing Longan Arillus. Processing methods should be selected according to the formula requirements， where no specific processing is indicated， the raw products is recommended for medicinal use.

Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease， and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine， proposes a new theory of “turbid toxin pathogenesis”， analyzes the scientific connotations of “turbid”， “toxin”， and the theory of “turbid toxin pathogenesis”， and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy， thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy， in order to provide a reference for the prevention and treatment of hepatic encephalopathy.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， harvesting and processing， and other aspects of Manjiao and Zanthoxyli Radix by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， in order to provide a basis for the development of famous classical formulas containing the two medicinal materials. According to the herbal textual research， Manjiao was first recorded in Shennong Bencaojing of the Han dynasty with aliases such as Zhujiao， Goujiao and Zhijiao. Throughout history， Manjiao was sourced from the stems and roots of Zanthoxylum armatum in the Rutaceae family， and its leaves and fruits can also be used in medicine. The traditional recorded production area was mainly in Yunzhong（now Tuoketuo region in Inner Mongolia）， with mentions in Zhejiang， Hunan， Fujian， Guangdong， Guangxi， Yunnan， Taiwan， and other provinces. Presently， this species is distributed from the south of Shandong， to Hainan， Taiwan， Tibet and other regions. The roots can be harvested year-round， while the fruits are harvested in autumn after maturity. In ancient times， the roots and stems were mostly used for brewing or soaking in wine， whereas nowadays， the roots are often sliced and then used as a raw material in traditional Chinese medicine， and the fruits should be stir-fried before use. Manjiao has a bitter taste and warm property， and was historically used to treat wind-cold dampness， joint pain， limb numbness， and knee pain. Modern researches have summarized its effects as dispelling wind， dispersing cold， promoting circulation， and relieving pain， and it is used for treating rheumatoid arthritis， toothache， bruises， as well as an anthelmintic. Zanthoxyli Radix initially known as Rudi Jinniugen， recorded in Bencao Qiuyuan of the Qing dynasty， with the alternate name of Liangbianzhen. In recent times， it is more commonly referred to as Liangmianzhen， sourced from the dried roots of Z. nitidum of the Rutaceae family， mainly produced in Guangxi and Guangdong. It can be harvested throughout the year， cleaned， sliced， and dried after harvesting. Zanthoxyli Radix is pungent， bitter， warm and slightly toxic， with the functions of promoting blood circulation， removing stasis， relieving pain， dispelling wind， and resolving swelling. Based on the results of herbal textual research， it is clarified that the ancient Manjiao and the modern Zanthoxyli Radix are not the same species. This article corrects the mistaken belief of by previous scholars that Zanthoxyli Radix is the same as ancient Manjiao， and suggests that formulas described as Manjiao should use Z. armatum as the medicinal herb， while those described as Liangmianzhen or Rudi Jinniu should use Z. nitidum. The processing was performed according to the processing requirements prescribed in the formulas， otherwise， the raw products are recommended for use.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， harvesting and processing， and other aspects of Manjiao and Zanthoxyli Radix by referring to the herbal medicine， medical books， prescription books and other documents of the past dynasties， combined with the relevant modern research materials， in order to provide a basis for the development of famous classical formulas containing the two medicinal materials. According to the herbal textual research， Manjiao was first recorded in Shennong Bencaojing of the Han dynasty with aliases such as Zhujiao， Goujiao and Zhijiao. Throughout history， Manjiao was sourced from the stems and roots of Zanthoxylum armatum in the Rutaceae family， and its leaves and fruits can also be used in medicine. The traditional recorded production area was mainly in Yunzhong（now Tuoketuo region in Inner Mongolia）， with mentions in Zhejiang， Hunan， Fujian， Guangdong， Guangxi， Yunnan， Taiwan， and other provinces. Presently， this species is distributed from the south of Shandong， to Hainan， Taiwan， Tibet and other regions. The roots can be harvested year-round， while the fruits are harvested in autumn after maturity. In ancient times， the roots and stems were mostly used for brewing or soaking in wine， whereas nowadays， the roots are often sliced and then used as a raw material in traditional Chinese medicine， and the fruits should be stir-fried before use. Manjiao has a bitter taste and warm property， and was historically used to treat wind-cold dampness， joint pain， limb numbness， and knee pain. Modern researches have summarized its effects as dispelling wind， dispersing cold， promoting circulation， and relieving pain， and it is used for treating rheumatoid arthritis， toothache， bruises， as well as an anthelmintic. Zanthoxyli Radix initially known as Rudi Jinniugen， recorded in Bencao Qiuyuan of the Qing dynasty， with the alternate name of Liangbianzhen. In recent times， it is more commonly referred to as Liangmianzhen， sourced from the dried roots of Z. nitidum of the Rutaceae family， mainly produced in Guangxi and Guangdong. It can be harvested throughout the year， cleaned， sliced， and dried after harvesting. Zanthoxyli Radix is pungent， bitter， warm and slightly toxic， with the functions of promoting blood circulation， removing stasis， relieving pain， dispelling wind， and resolving swelling. Based on the results of herbal textual research， it is clarified that the ancient Manjiao and the modern Zanthoxyli Radix are not the same species. This article corrects the mistaken belief of by previous scholars that Zanthoxyli Radix is the same as ancient Manjiao， and suggests that formulas described as Manjiao should use Z. armatum as the medicinal herb， while those described as Liangmianzhen or Rudi Jinniu should use Z. nitidum. The processing was performed according to the processing requirements prescribed in the formulas， otherwise， the raw products are recommended for use.

Hepatic encephalopathy （HE） is a common complication of severe liver disease in the end stage， and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation， and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora， short-chain fatty acids （SCFAs） play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways， thereby playing an important role in the diagnosis， treatment， and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs， this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE， in order to provide new ideas for optimizing clinical prevention and treatment strategies.

ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills （STDP） ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats， which were then allocated into sham， model， STDP， and telmisartan （TLM） groups and treated for 21 days. The heart function was detected by echocardiography， and the levels of myocardial injury markers， nitric oxide （NO）， endothelin-1 （ET1）， and angiotensinⅡ （AngⅡ） were determined by enzyme-linked immunosorbent assay （ELISA）. The protein levels of endothelial nitric oxide synthase （eNOS） and inducible nitric oxide synthase （iNOS） were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum （5%， 10%， and 20%） for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS， iNOS， angiotensin-converting enzyme 2 （ACE2）， and angiotensinⅡ receptor 2 （AT2）. MLN-4760， an ACE2 inhibitor， was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group， the model group showed decreases in left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.05）， a decline in serum NO level， elevations in serum AngⅡ and ET1 levels， a reduction in p-eNOS/eNOS ratio， and up-regulation in iNOS expression （P<0.05）. Compared with the model group， STDP increased LVEF， LVFS， and cardiac output （P<0.05）， raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum （P<0.05）， increased the p-eNOS/eNOS value， and inhibited iNOS expression （P<0.05）. Compared with the AngⅡ group， STDP increased the NO content and decreased the ET1 content in endothelial cells （P<0.05）， increased the p-eNOS/eNOS ratio， and inhibited the iNOS expression （P<0.05）. The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS， eNOS， and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure， enhances the synthesis and release of NO in cardiac microvascular endothelial cells， reduces AngⅡ and ET1 levels， and regulates the expression of p-eNOS and eNOS， thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.

Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, β-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma's active components in cancer treatment.

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*