A comprehensive review of the botany, phytochemistry, pharmacology, and toxicology of Murrayae Folium et Cacumen.

Ethnopharmacological relevance: Murrayae Folium et Cacumen (MFC) is a plant considered to be a traditional Chinese medicine with culinary value as well. The dry leaves and twigs of Murraya paniculata and M. exotica are used to treat stomach aches, rheumatism, toothaches, swelling, and insect and snake bites. They are also used to prepare spicy chicken dishes. Aim of the review: This review comprehensively summarizes the available information on the botanical characterization, phytochemistry, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC. Methods: Relevant scientific literature up to August 2023 was included in the study. Chinese and English studies on MFC were collected from databases, including PubMed, Elsevier, Web of Science, Springer, Science Direct, Wiley, ACS, and CNKI (Chinese). Doctoral and Master's dissertations were also included. Results: In total, 720 compounds have been identified and reported in the literature, including flavonoids, coumarins, alkaloids, sterols, phenylpropenols, organic acids, spirocyclopentenones, and volatile oils. Flavonoids and coumarins are the two most important bioactive compounds responsible for these pharmacological activities. MFC has anti-inflammatory, anti-bacterial, anti-microbial, anti-diabetic, anti-tumor, anti-oxidant, anti-depressant, potential anti-Alzheimer's disease, chondroprotective, and analgesic properties. The pharmacological effects include interrupting the STAT3/NF-κB/COX-2 and EGFR signaling pathways, downregulating EpCAM expression, inhibiting NF-κB and ERK signals, inhibiting the EP/cAMP/PKA signaling pathway and miR-29a/Wnt/ß-catenin signaling activity, and upregulating Foxo3a expression. Conclusion: This review demonstrates that the chemical constituents, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC support its use in traditional Chinese botanical medicines. MFC contains a wide range of chemical compounds. Flavonoids and coumarins promote strong pharmacological activity and, are low-toxicity natural phytomedicines that are widely used in medicine, food, ornamentation, and cosmetics, making MFC a promising compound for development and use in the treatment of several medical conditions.

Research progress of plant-derived natural alkaloids in central nervous system diseases.

Central nervous system (CNS) disease is one of the most important causes of human death. Because of their complex pathogenesis, more and more attention has been paid to them. At present, drug treatment of the CNS is the main means; however, most drugs only relieve symptoms, and some have certain toxicity and side effects. Natural compounds derived from plants can provide safer and more effective alternatives. Alkaloids are common nitrogenous basic organic compounds found in nature, which exist widely in many kinds of plants and have unique application value in modern medicine. For example, Galantamine and Huperzine A from medicinal plants are widely used drugs on the market to treat Alzheimer's disease. Therefore, the main purpose of this review is to provide the available information on natural alkaloids with the activity of treating central nervous system diseases in order to explore the trends and perspectives for the further study of central nervous system drugs. In this paper, 120 alkaloids with the potential effect of treating central nervous system diseases are summarized from the aspects of sources, structure types, mechanism of action and structure-activity relationship.

Traditional uses, phytochemistry, pharmacology, and toxicity of Eriobotrya japonica leaves: A summary.

ETHNOPHARMACOLOGICAL RELEVANCE: Eriobotrya japonica Lindl. has been included in "The Plant List" (http://www.theplantlist.org) and is the most widely researched species in its genus. E. japonica is a subtropical evergreen fruit tree belonging to the Rosaceae family. Its dried leaves are widely used in traditional Chinese herbal medicine to treat coughing caused by pulmonary inflammation, dyspnea due to asthma and cough, nausea caused by stomach disorders, restlessness, and thirst. Furthermore, it is used to treat stomach ache, ulcers, chronic bronchitis, cancer, and diabetes mellitus in Japanese folk medicine. However, no systematic reports on E. japonica leaves have been published before. AIM OF THE STUDY: This review summarizes the available information on the traditional uses, phytochemistry, pharmacology, toxicity, and quality control of various extracts and phytoconstituents of E. japonica leaves. MATERIALS AND METHODS: Relevant publications between 1931 and 2022 were considered. Chinese and English studies on E. japonica leaves were collected from databases, including PubMed, Web of Science, Elsevier, ACS Publications, Springer, and CNKI (Chinese). The traditional uses, phytochemistry, pharmacology, toxicity, and quality control of E. japonica leaves were reviewed. RESULTS: Briefly, 164 compounds, including triterpenes, flavonoids, sesquiterpene glycosides, megastigmane derivatives, phenylpropanoids, and organic acids, have been identified from E. japonica leaves, in addition to 169 volatile oils. More than half of these compounds have not yet been reported to have pharmacological activities. Triterpenes and flavonoids are the most important bioactive compounds responsible for pharmacological activities, such as antidiabetic, anti-inflammatory, and antitumor activities. Other beneficial physiological effects such as antioxidant, hepatoprotective, bronchodilatory, antitussive, and expectorant effects and tracheal smooth muscle relaxation, protection against myocardial ischemia injury, and improved cognitive activities have also been reported. High doses of E. japonica leaf extracts have been used in laboratory animals, and no side effects or toxicity-symptoms have been observed. CONCLUSIONS: The pharmacological activities of E. japonica leaves support their use in traditional Chinese herbal medicine. However, several aspects, such as the bioavailability, pharmacodynamics, pharmacokinetics, mechanism of action, and structure-activity relationships of the pure compounds isolated from E. japonica leaves, have not been studied yet and warrant further studies.

Effects of Huangkui Capsule on the Expression of SPARC in the Kidney Tissue of a Rat Model with Diabetic Nephropathy.

OBJECTIVE: The objective of the research is to investigate the effects of Huangkui capsule on the expression of SPARC in the kidney tissues of diabetic nephropathy. METHODS: SD rats were divided into three groups: normal control group, untreated DN group and HKC-treated DN group. The therapeutic effects and underlying molecular mechanism of HKC on DN rats induced by streptozotocin were evaluated by the levels of serum creatinine, blood urea nitrogen, 24-hour urinary protein and the expression of SPARC. Pathological changes in kidney tissues were observed through hematoxylin-eosin (HE) staining. Moreover, western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to detect the variation of SPARC. RESULTS: This study was performed to investigate the effects of HKC on DN in SD rats model and its molecular mechanism. Our results showed that the rats treated with HKC had an improved general state and reduced creatinine, blood urea nitrogen and 24-hour urinary protein levels. The deterioration of renal function was delayed due to treatment with HKC. HE staining was utilized to observe that HKC can improve histopathological findings in the kidney tissues of DN rats, including kidney fibrosis. Results of western blot and qRT-PCR showed that HKC can inhibit the expressions of SPARC in the rat model of DN. CONCLUSION: The present findings demonstrated that HKC inhibited SPARC level and had significant therapeutic effects on DN.

The Modified Bushen Antai Recipe Upregulates Estrogen and Progesterone Receptors at the Maternal-Fetal Interface in Pregnant Rats with Mifepristone-Induced Pregnancy Loss.

BACKGROUND: The modified Bushen Antai recipe (BSAT) is a centuries-old traditional Chinese medicine that we use in our center as a therapy against pregnancy loss. Our study aimed to explore the potential benefit and mechanism of BSAT in pregnant rats with mifepristone-induced pregnancy loss. MATERIALS AND METHODS: The signature compounds of the eight BSAT ingredients were analyzed by high-performance liquid chromatography (HPLC). The BSAT group (n = 8) was treated daily with 6.3 ml/kg BSAT from gestation day (D) 0.5 to 10.5 and once with 1.25 mg/kg mifepristone on D 10.5. Normal saline replaced BSAT in the model group (n = 8), and both BSAT and mifepristone in the control group (n = 8). Morphological and histological analyses were performed on D 13.5. RESULTS: BSAT contains eight medicinal ingredients including Cuscuta chinensis and Dipsacus asperoides. The HPLC analysis detected the signature compounds of seven medicinal ingredients in the extract. Embryo resorption rate in the BSAT group was significantly lower than that in the model group, although the number of surviving embryos was similar between the two groups. Hematoxylin and eosin (HE) staining suggested that the maximum cross-sectional area of the placenta and the area ratio of the placental labyrinth in the BSAT group were higher than those in the model group. Immunohistochemical (IHC) staining indicated that the expression of ki67, estrogen receptor alpha (ERα), and progesterone receptor (PR) in the placental labyrinth of the BSAT group was higher than that of the model group. Furthermore, the protein levels of ERα, PR, phospho-Akt/Akt, and phospho-Erk1/2/Erk1/2 in the BSAT group were higher than those in the control group. The mRNA levels of ERα and PR in the BSAT group were higher than those in the control group. CONCLUSIONS: BSAT may induce estrogen and progesterone receptors by phosphorylation via the classic Akt and Erk1/2 signaling pathways in the maternal-fetal interface of pregnant rats, thereby reducing the pregnancy loss rate and improving the live birth rate.

Circulating vitamin E levels and Alzheimer's disease: a Mendelian randomization study.

Alzheimer's disease (AD) is the leading cause of dementia in older adults. It is more than 50 years since vitamin E was recognized as critical for optimal neurological health. Clinical studies have yielded inconsistent findings on the effect of vitamin E on AD risk. Thus, it remains unclear whether vitamin E levels are genetically associated with AD risk. We performed a Mendelian randomization study to investigate association of circulating vitamin E levels with AD using large-scale vitamin E genome-wide association study data set (N = 7781 individuals of European descent) and AD genome-wide association study data set (N = 54,162 individuals [including 17,008 AD cases and 37,154 controls of European descent]). Mendelian randomization-Egger intercept test showed no significant pleiotropy (ß = -0.113; p = 0.296). Inverse-variance weighted (odds ratio = 0.96, 95% confidence interval: 0.47-1.94, p = 0.936) and weighted median analyses (odds ratio = 1.13, 95% confidence interval: 0.35-3.69, p = 0.836) showed no significant association between vitamin E and AD. Together with previous literature, this suggests that vitamin E supplementation may not forestall AD in the general population.

Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study.

Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application.

A New Triterpenoid from the Aerial Parts of Agrimonia pilosa.

(1S,3R,17R,18R,19R,20R,22R)-1,3,19,22-tetrahydroxy-28-norurs-12-en-2-one (1), along with 5 known triterpenoids (2-6), were isolated from the aerial parts of Agrimonia pilosa Ledeb. Their structures were established based on extensive spectroscopic and MS analysis. The absolute configuration of compound 1 was deduced by circular dichroism (CD). Compound 1 was the first example of a 28-norursene backbone isolated from the genus Agrimonia. Compounds 2-6 were tested for anti-inflammatory activities against RAW 264.7 macrophages. A plausible biosynthetic pathway for compound 1 in A. pilosa was also proposed.

Deep sequencing identifies tissue-specific microRNAs and their target genes involving in the biosynthesis of tanshinones in Salvia miltiorrhiza.

Salvia miltiorrhiza is one of the most popular traditional medicinal herbs in Asian nations. Its dried root contains a number of tanshinones, protocatechuic aldehyde, salvianolic acid B and rosmarinic, and is used for the treatment of various diseases. The finding of microRNAs (miRNAs) and their target genes will help understand their biological role on the biosynthesis of tanshinones in S. miltiorrhiza. In the present study, a total of 452 known miRNAs corresponding to 589 precursor miRNAs (pre-miRNAs), and 40 novel miRNAs corresponding to 24 pre-miRNAs were identified in different tissues of S. miltiorrhiza by high-throughput sequencing, respectively. Among them, 62 miRNAs express only in root, 95 miRNAs express only in stem, 19 miRNAs express only in leaf, and 71 miRNAs express only in flower, respectively. By the degradome analysis, 69 targets potentially cleaved by 25 miRNAs were identified. Among them, acetyl-CoA C-acetyltransferase was cleaved by miR5072, and involved in the biosynthesis of tanshinones. This study provided valuable information for understanding the tissue-specific expression patterns of miRNAs in S. miltiorrhiza, and offered a foundation for future studies of the miRNA-mediated biosynthesis of tanshinones.

Hypolipidemic effect of gypenosides in experimentally induced hypercholesterolemic rats.

BACKGROUND: To investigate the anti-hyperlipidemic effect of gynosaponins (GPs) in hyperlipidemic rats induced by high lipid diet. METHODS: Animal model of hyperlipidemia was established by high-fat and high-cholesterol diet. Rats were randomly divided into 6 groups, except the normal and model groups, rats in GPs groups were daily administered intragastrically with GPs (50, 100, and 200 mg/kg), and rats in simvastatin group were daily administered intragastrically with simvastatin (10 mg/kg). It was measured that the contents of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in the serum, TG and TC in the liver during this experiment, respectively. The left lobe of liver was observed by histopathological staining, and the immunohistochemical staining was used to observe the effects on the effect of GPs on liver functions. RESULTS: Compared with the model group, GPs groups could remarkably decrease the content of lipids, GSH-Px, SOD, CAT and MDA in the serum and TC and TG in the liver of the hyperlipidemic rats. The pathomorphological results of hepatic tissue showed that fatty degeneration and inflammatory reaction of GPs groups were lightened compared with the model group. CONCLUSIONS: The results show that GPs has good effects on the treatment of hyperlipidemia induced by high lipid diet in rats. The possible anti-hyperlipidemia mechanism maybe those GPs can regulate the disorder of lipid metabolism as well as ameliorate hepatic function.

[Microscopic quantitative study on Saiga tatarica in "lingyang qing fei pill"].

OBJECTIVE: To determine Saiga tatarica content in "Lingyang Qing Fei Pill". METHODS: Volumetric analysis combined with quantitative microscopy was used to determine Saiga tatarica content by sample itself as standard substance. RESULT AND CONCLUSION: The method of determining the content of Saiga tatarica is simple and creditable.