Chrysosaxillins A-E, cucurbitane triterpenoid derivatives from Chrysosplenium axillare Maxim. (Yajima) and their cytotoxic activities.

Chrysosplenium axillare Maxim. is used in traditional Tibetan medicine for the treatment of various human diseases, such as fever, headache, cholecystitis, acute icterohepatitis and acute liver necrosis. In this study, five new cucurbitane triterpenoid derivatives, chrysosaxillins A-E (1-5), along with three known structurally related compounds (6-8) have been isolated from whole herb of C. axillare. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR, HRESIMS, UV, IR, ECD and single-crystal X-ray diffraction. All isolates were evaluated for cytotoxic activities against four tumor cell lines including PC-3, A549, MCF-7, and HepG2. The results discovered that compound 1 possessed the most potent cytotoxicity against A549 cells with IC50 value of 0.05 µM, while compounds 2 and 4 have mild cytotoxicities against cells tested with IC50 values ranging from 8.78 to 41.72 µM. Our study suggests that C. axillare might serve as a valuable source of cucurbitane triterpenoids potentially useful for the development of new anti-tumor agents and support its use as a crop benefits to local economic.

A Review of Traditional Use, Constituent Analysis, Bioactivity, and Application of Volatile Oils from Elsholtzia.

BACKGROUND: Elsholtzia belongs to the Labiatae family, which consists of herbaceous subshrubs and shrubs. Among them, volatile oils are an important chemical component in Elsholtzia, which have various bioactive medicinal and developmental values. METHODS: The references about volatile oils of Elsholtzia in this review were obtained from Web of Science, SciFinder, PubMed, Willy, Elsevier, SpringLink, ACS publications, Google Scholar, Baidu Scholar, Scopus, and CNKI. The other information about Elsholtzia was obtained from classical works or ancient books. RESULTS: Traditionally, the volatile oils from Elsholtzia were used in Chinese medicine to treat cholera, abdominal pain, vomiting, and scattered edema. Relevant research revealed that Elsholtzia contains many different types of volatile oils, and most of them display bioactivities, including anti-oxidant, anti-bacterial, anti-viral, hypolipidemic, insecticidal, and antiinflammatory activities, treating spleen and stomach. Furthermore, the applications of volatile oils were summarized and analyzed in this paper. CONCLUSION: The contents of traditional use, constituent analysis, bioactivity, and application of volatile oils from Elsholtzia were reviewed in this paper. This will provide important research value and a scientific basis for the in-depth study of the plants of Elsholtzia in the future.

Phyllanthus emblica Linn: A comprehensive review of botany, traditional uses, phytonutrients, health benefits, quality markers, and applications.

Phyllanthus emblica Linn is not only an edible fruit with high nutritional value, but also a medicinal plant with multiple bioactivities. It is widely used in clinical practice with functions of clearing heat, cooling blood, digesting food, strengthening stomach, promoting fluid production, and relieving cough. This review summarized a wide variety of phytonutrients, including nutritional components (mineral elements, amino acids, vitamins, polysaccharides, unsaturated free fatty acids) and functional components (phenolic acids (1-34), tannins (35-98), flavonoids (99-141), sterols (142-159), triterpenoids (160-175), lignans (176-183), alkaloids (184-197), alkanes (198-212), aromatic micromolecules (213-222), other compounds (223-239)). The isolated compounds and the various extracts of P. emblica Linn presented a diverse spectrum of biological activities such as anti-oxidant, anti-cancer, anti-inflammatory, anti-bacterial, hepatoprotective, hypoglycemic, anti-atherosclerosis, neuroprotective, enhancing immunity, anti-fatigue, anti-myocardial fibrosis. The quality markers of P. emblica Linn were predicted and analyzed based on traditional medicinal properties, traditional efficacy, plant genealogy and chemical component characteristics, biogenic pathway of chemical components, measurability of chemical components, transformation characteristics of polyphenolic components, homologous characteristics of medicine and food, compound compatibility environment, and clinical applications. This review also summarized and prospected applications of P. emblica Linn in beverages, preserved fruits, fermented foods, etc. However, the contents of mechanism, structure-activity relationship, quality control, toxicity, extraction, processing of P. emblica Linn are not clear, and are worth further studies in the future.

The sources, properties, extraction, biosynthesis, pharmacology, and application of lycopene.

Lycopene is an important pigment with an alkene skeleton from Lycopersicon esculentum, which is also obtained from some red fruits and vegetables. Lycopene is used in the food field with rich functions and serves in the medical field with multiple clinical values because it has dual functions of both medicine and food. It was found that lycopene was mainly isolated by solvent extraction, ultrasonic-assisted extraction, supercritical fluid extraction, high-intensity pulsed electric field-assisted extraction, enzymatic-assisted extraction, and microwave-assisted extraction. Meanwhile, it was also obtained via 2 synthetic pathways: chemical synthesis and biosynthesis. Pharmacological studies revealed that lycopene has anti-oxidant, hypolipidemic, anti-cancer, immunity-enhancing, hepatoprotective, hypoglycemic, cardiovascular-protective, anti-inflammatory, neuroprotective, and osteoporosis-inhibiting effects. The application of lycopene mainly includes food processing, animal breeding, and medical cosmetology fields. It is hoped that this review will provide some useful information and guidance for future study and exploitation of lycopene.

Development of novel salicylic acid-donepezil-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid-donepezil-rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC50 = 0.53 µM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.

Vicatia thibetica de Boiss: Botany, Traditional Uses, Phytochemistry, Quantitative Analysis, and Pharmacology.

BACKGROUND: Vicatia thibetica de Boiss is a common Tibetan medicine used for both medicine and food, belonging to the family Apiaceae. This plant has the functions of dispelling wind, removing dampness, dispersing cold, and relieving pain. It has great development potential and application prospects in food development and medicinal value. METHODS: The related references on botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of V. thibetica de Boiss had been retrieved from both online and offline databases, including PubMed, ScienceDirect, Web of Science, Elsevier, Willy, SpringLink, SciFinder, Google Scholar, Baidu Scholar, ACS publications, SciHub, Scopus, and CNKI. RESULTS: V. thibetica de Boiss exerts nourishing, appetizing, and digestive effects according to the theory of Tibetan medicine. Phytochemical reports have revealed that V. thibetica de Boiss contains flavonoids, coumarins, sterols, and organic acids. Meanwhile, the quantitative analysis of the chemical constituents of V. thibetica de Boiss has been done by means of UPLC-Q-TOF-MS. It has also been found that V. thibetica de Boiss possesses multiple pharmacological activities, including anti-fatigue, anti-oxidant, anti-aging, and non-toxic activities. CONCLUSION: This paper has comprehensively summarized botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of V. thibetica de Boiss. It will not only provide an important clue for further studying V. thibetica de Boiss, but also offer an important theoretical basis and valuable reference for in-depth research and exploitation of this plant in the future.

A Comprehensive Review of Structures, Structure-activity Relationships, Extractions, and Bioactivities of Flavonoids from Citrus medica.

BACKGROUND: Citrus medica is a kind of medicinal and edible plant. It not only contains rich nutrients but also has a variety of therapeutic functions, including relieving pain, harmonizing the stomach, removing dampness, reducing phlegm, cleaning the liver, and relieving qi in traditional Chinese diagnosis. METHODS: The references of C. medica were mainly collected from the online database, such as PubMed, SciFinder, Web of Science, Google Scholar, Elsevier, Willy, SpringLink, and CNKI. The other related references were sorted by consulting books and documents. RESULTS: This review summarized and analyzed the different types of flavonoids of C. medica, including flavone-O-glycosides, flavone-C-glycosides, dihydroflavone-O-glycosides, flavonol aglycones, flavonoid aglycones, dihydroflavonoid aglycones, and bioflavonoids. The extraction methods of flavonoids were summarized in this review. Meanwhile, the multiple bioactivities of these flavonoids, including anti-atherosclerotic, hypolipidemic, anti-oxidant, hypoglycemic, and other activities. Their structure-activity relationships were reviewed and discussed in this paper. CONCLUSIONS: This review summarized the different extraction methods of diverse flavonoids with multiple bioactivities of C. medica, and their structure-activity relationships were discussed in this paper. This review may provide a valuable reference for researching and exploiting C. medica.

Hippophae rhamnoides L.: A Comprehensive Review on the Botany, Traditional Uses, Phytonutrients, Health Benefits, Quality Markers, and Applications.

Hippophae rhamnoides L. (sea buckthorn), consumed as a food and health supplement worldwide, has rich nutritional and medicinal properties. Different parts of H. rhamnoides L. were used in traditional Chinese medicines for relieving cough, aiding digestion, invigorating blood circulation, and alleviating pain since ancient times. Phytochemical studies revealed a wide variety of phytonutrients, including nutritional components (proteins, minerals, vitamins, etc.) and functional components like flavonoids (1-99), lignans (100-143), volatile oils (144-207), tannins (208-230), terpenoids (231-260), steroids (261-270), organic acids (271-297), and alkaloids (298-305). The pharmacological studies revealed that some crude extracts or compounds of H. rhamnoides L. demonstrated various health benefits, such as anti-inflammatory, antioxidant, hepatoprotective, anticardiovascular disease, anticancer, hypoglycemic, hypolipidemic, neuroprotective, antibacterial activities, and their effective doses and experimental models were summarized and analyzed in this paper. The quality markers (Q-markers) of H. rhamnoides L. were predicted and analyzed based on protobotanical phylogeny, traditional medicinal properties, expanded efficacy, pharmacokinetics and metabolism, and component testability. The applications of H. rhamnoides L. in juice, wine, oil, ferment, and yogurt were also summarized and future prospects were examined in this review. However, the mechanism and structure-activity relationship of some active compounds are not clear, and quality control and potential toxicity are worth further study in the future.

Ethnopharmacology, Phytochemistry, and Pharmacology of Pyrethrum tatsienense (Bureau & Franch.) Ling ex C. Shih: A Comprehensive Review.

BACKGROUND: Pyrethrum tatsienense (Bureau & Franch.) Ling ex C. Shih (PTLCS) belongs to the family Compositae, which is a perennial medicinal plant mainly distributed in the Qinghai-Tibet Plateau of China. This review provides a comprehensive summary of the ethnopharmacology, phytochemistry, and pharmacology of PTLCS. This review offers valuable references and guidance for researching PTLCS in depth. METHODS: The related references of PTLCS were retrieved from an online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. RESULTS: PTLCS is widely reported for treating headaches, head injuries, traumatic injuries, anabrosis, impetigo, hepatitis, and other diseases in the medical field. Phytochemical research revealed that this plant contained flavonoid aglycones, flavonoid glycosides, xanthones, triterpenoids, coumarins, polyacetylenes, volatile oils, and other compounds. Meanwhile, PTLCS exhibited extensive pharmacological activities including anti-cardiac ischemia, anti-hypoxia, hepatoprotective, anti- inflammatory and analgesic, and antioxidant activities. CONCLUSIONS: PTLCS is widely used as a Tibetan medicine, which has a variety of chemicals with diverse bioactivities. Therefore, further studies are necessary to perform on the PTLCS to assay biological activities, discover their bioactive constituents, and reveal pharmacological mechanisms. This review may supply an important theoretical basis and valuable reference for in-depth research and exploitations of PTLCS.

Ethnopharmacology, Phytochemistry, and Pharmacology of Highland Barley Monascus purpureus Went: A Comprehensive Review.

BACKGROUND: Highland barley Monascus purpureus Went, a traditional Tibetan medicine with food functions, which is fermented by Monascus purpureus with highland barley as substrate. It possesses various medical functions of promoting blood circulation and removing blood stasis, invigorating spleen and promoting digestion in folk of the Qinghai-Tibet Plateau in China. This review provides a comprehensive overview of ethnopharmacology, phytochemistry, and pharmacology of highland barley Monascus purpureus Went. METHODS: The references of highland barley Monascus purpureus Went were retrieved from the online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. RESULTS: Phytochemical research revealed that highland barley Monascus purpureus Went contained multiple chemical components, including Monascus pigments, monacolins, lactones, and other compounds. The reported pharmacological activities of highland barley Monascus purpureus Went included hypolipidemic, anti-nonalcoholic fatty liver disease, and hepatoprotective activities. CONCLUSION: In a word, botany, ethnopharmacology, phytochemistry and pharmacology of highland barley Monascus purpureus Went were reviewed comprehensively in this paper. In the future, highland barley Monascus purpureus Went needs further study, such as paying more attention to quality control and utilization of medicine. Therefore, this review may provide a theoretical basis and valuable data for future studies and exploitations on highland barley Monascus purpureus Went.

Lipskynoids A-G, New Acyclic Diterpenes from the Flowers of Carpesium lipskyi.

Seven new acyclic diterpenes, namely lipskynoids A-G (1-7), were isolated from the flowers of Carpesium lipskyi, a traditional Tibetan herbal medicine with anti-inflammatory and antipyretic-analgesic effects. These new compounds were elucidated by analysis of extensive spectroscopic data including ESI-MS, 1D, 2D NMR, and DP4+ analyses. Biological assays showed that 1-7 display significant inhibitory effects against the NO production in LPS-induced RAW264.7 cells with its IC50 values from 9.9 to 18.47 µM, however, no cytotoxicity effect was observed of these isolates against the growth of HePG2, PC3, DU145, and A549 cells.

Isolation and characterization of auronlignan derivatives with hepatoprotective and hypolipidemic activities from the fruits of Hippophae rhamnoides L.

The fruit of Hippophae rhamnoides L. is not only used as delicious food with nutritional values, but also served as traditional Chinese medicine with multiple bioactivities. In order to find structurally interesting and bioactive isolates from the fruits of H. rhamnoides L., a bioassay-guided investigation was applied to seek the hepatoprotective and hypolipidemic ingredients in this study. As a result, three new (10 → 10'')-biauronlignans (1-3), three new 10-(4''-hydroxy-benzyl)-auronlignans (4-6), three new 10-O-ß-D-glucopyranosyl-auronlignans (7-9), and eleven known auronlignan derivatives (10-20) were isolated from the fruits of H. rhamnoides L. for the first time, and their structures were determined by extensive and comprehensive IR, UV, NMR, MS spectral analyses and compared with the reported references. Among them, compounds 1, 4, 7, 11, 15, and 19 showed moderate hepatoprotective activities against the damage in acetaminophen-induced HepG2 cells; compounds 2, 5, 8, and 12 exhibited moderate inhibition of pancreatic lipase activity, and decreased the moderately FFA-induced lipid accumulation in HepG2 liver cells. The plausible biogenetic pathway and preliminary structure-activity relationship of the selected compounds are scientifically summarized and discussed in this study.

Antidepressant alkaloids from the rhizomes of Corydalis decumbens.

Two new alkaloids (1 and 2), named 1,7-dimethoxy-2'-prenyl-1',9-dihydropyrrolo-carbazole (1) and 1,7-dimethoxy-4',5'-dimethylcyclopenta-carbazole-1',3'-dione (2), along with thirteen known alkaloids (3-15) were isolated by means of silica gel, sephadex LH-20, and semi-preparative HPLC from the CHCl3 extraction of Corydalis decumbens for the first time. Their structures were determined by NMR, MS, IR, UV, and related references. Compounds (1-15) were evaluated for their antidepressant activities by measuring inhibition of monoamine neurotransmitter reuptake in vitro. Among them, compounds 1, 2, 4, and 6 showed certain antidepressant activities.

Establishment and metabonomics analysis of nonalcoholic fatty liver disease model in golden hamster.

The aim is to establish a model of nonalcoholic fatty liver disease (NAFLD) caused by feeding with high-fat, high-fructose, and high-cholesterol diet (HFFCD) in golden hamsters, and to investigate the characteristics of the NAFLD model and metabolite changes of liver tissue. Golden hamsters were fed HFFCD or control diets for six weeks. Body weight, abdominal fat index, and liver index was assessed, serum parameters, hepatic histology, and liver metabolites were examined. The results showed that body weight, abdominal fat, and liver index of hamsters were significantly increased in the model group, the level of serum total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C) were significantly increased in model group as well, and high density lipoprotein-cholesterol (HDL-C) was significantly decreased. In addition, lipid deposition in liver tissue formed fat vacuoles of different sizes. Metabonomics analysis of the liver showed that the metabolic pathways of sphingolipid, glycerophospholipids, and arginine biosynthesis were disordered in the NAFLD model. The modeling method is simple, short time, and uniform. It can simulate the early fatty liver caused by common dietary factors, and provides an ideal model for the study of the initial pathogenesis and therapeutic drugs for NAFLD.

Two Olean-27-carboxylic Acid-Type Triterpenoids as Chemical Markers Isolated from Saxifraga umbellulata.

Two olean-27-carboxylic acid-type triterpenoids (1 and 2) were isolated from Saxifraga umbellulata (Saxifragaceae), representing the first case in the chemical discoveries of genus Saxifraga. Compound 1 was determined to be a new compound named 'Saxifragic acid' based on the comprehensive spectroscopic and X-ray crystallographic analyses. Compound 2 (deacetylated saxifragic acid) is a known compound reported before, but its absolute configuration through X-ray crystallographic analyses was first described here. In addition, their cytotoxicity against five digestive human cancer cell lines (BGC-823, GBC-SD, CCC-9810, HT-29, and HepG2) and hepatoprotective activity against CCl4 -induced L-o2 cell injury in vitro were evaluated. Interestingly, UPLC-QTOFMS analysis showed that these two compounds could be used as chemical markers to discriminate between S. umbellulata and S. tangutica, both of which are used for the treatment of hepatobiliary diseases in traditional Tibetan medicine.

Dataset for liver metabolomic profile of highland barley Monascus purpureus went extract-treated golden hamsters with nonalcoholic fatty liver disease.

Nonalcoholic Fatty Liver Disease (NAFLD) is a serious problem endangering human health in the world. The pathogenesis of this disease is often accompanied by lipid metabolism disorder and can cause liver lipid accumulation. Highland barley Monascus purpureus Went extract (HBMPWE) can inhibit the liver lipid accumulation caused by a high-fat, high-fructose, high-cholesterol diet. However, it is not clear what changes have taken place in the process of liver lipid metabolism after HBMPWE administration. To fill this knowledge gap and to support the findings published in the companion research article entitled "Highland Barley Monascus purpureus Went Extract Ameliorates High-Fat, High-Fructose, High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism in Golden Hamsters" [1], we provided important information related to the liver differential metabolites and identified twenty-one differential metabolites of liver metabolism. In the model group, the levels of lactate, linoleic acid, and malic acid increased significantly. After HBMPWE treatment, the expressions of these metabolites reduced significantly. Therefore, these liver differential metabolites could be used as biological signatures reflecting the severity of NAFLD and HBMPWE treatment outcomes.

Structurally diverse Monascus pigments with hypolipidemic and hepatoprotective activities from highland barley Monascus.

Highland barley Monascus has historically been used in solid state fermentation and traditional fermented foods in Tibet. It is possessed of the characteristics of medicine and food. Three new 8,13-unsaturated benzocyclodiketone-conjugated Monascus pigments (1-3), three new benzofuran Monascus pigments (4-6), three new butylated malonyl Monascus pigments (7-9), and eleven known Monascus pigment derivatives (10-20) were isolated from highland barley Monascus for the first time. Their structures were determined by analyzing NMR, MS, UV, and IR spectral data and compared with relevant references. Among them, compounds 2, 4, 6 showed important inhibition of pancreatic lipase activity, and decreased significantly FFA-induced lipid accumulation in HepG2 liver cells. Additionally, compounds 1, 10, 14, 16, 18 exhibited certain hepatoprotective activities against the damage in acetaminophen-induced HepG2 cells. The plausible biogenetic pathway and preliminary structure activity relationship of the selected compounds were scientifically summarized and discussed in this work.

Highland barley Monascus purpureus Went extract ameliorates high-fat, high-fructose, high-cholesterol diet induced nonalcoholic fatty liver disease by regulating lipid metabolism in golden hamsters.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocyte lipid accumulation is the main feature in the early stage of nonalcoholic fatty liver disease (NAFLD). Highland barley Monascus purpureus Went (HBMPW), a fermentation product of Hordeum vulgare Linn. var. nudum Hook. f. has traditionally been used as fermented foods in Tibet with the effect of reducing blood lipid in folk medicine. AIM OF THE STUDY: This study investigated the protective effects and molecular mechanism of highland barley Monascus purpureus Went extract (HBMPWE) on NAFLD in syrian golden hamster fed with high-fat, high-fructose, high-cholesterol diet (HFFCD). MATERIALS AND METHODS: HFFCD-induced NAFLD golden hamster model was established and treated with HBMPWE. Liver index, biochemical index, and hematoxylin and eosin (HE) staining were observed. Liver metabolomics and western blot analysis were employed. RESULTS: Our study found that HBMPWE ameliorated HFFCD induced dyslipidemia, weight gain and elevated the liver index. In addition, HBMPWE treatment significantly attenuated lipid accumulation in the liver and modulated lipid metabolism (sphingolipid, glycerophospholipid). Our data demonstrated that HBMPWE not only regulated the expression of proteins related to fatty acid synthesis and decomposition (SREBP-1/ACC/FAS/AceS1, PPARα/ACSL/CPT1/ACOX1), but also regulated the expression of proteins related to cholesterol synthesis and clearance (HMGCR, LDLR, CYP7A1). CONCLUSIONS: HBMPWE improved NAFLD through multiple pathways and multiple targets in body metabolism and could be used as a functional food to treat NAFLD and other lipid metabolic disorders.

Structurally diverse biflavonoids from the fruits of Citrus medica L. var. sarcodactylis Swingle and their hypolipidemic and immunosuppressive activities.

The fruit of Citrus medica L. var. sarcodactylis Swingle is not only used as a traditional medicinal plant, but also served as a delicious food. Six new (3'→7″)-biflavonoids (1-6), and twelve known biflavonoid derivatives (7-18) were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. Their structures were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, and IR spectral data coupled with the data described in the literature. Compounds (1-18) were evaluated for their hypolipidemic activities with Orlistat as the positive control, and assayed for their immunosuppressive activities with Dexamethasone as the positive control, respectively. Among them, compounds (1-3) exhibited moderate inhibition of pancreatic lipase activity by inhibiting 68.56 ± 1.40%, 56.18 ± 1.57%, 53.51 ± 1.59% of pancreatic lipase activities at the concentration of 100 µM, respectively. Compounds (4-6) and 8 showed potent immunosuppressive activities with the IC50 values from 16.83 ± 1.32 to 50.90 ± 1.79 µM. The plausible biogenetic pathway and preliminary structure activity relationship of the selected compounds were scientifically summarized and discussed in this study.