Ethnopharmacology of Rubus idaeus Linnaeus: A critical review on ethnobotany, processing methods, phytochemicals, pharmacology and quality control.

ETHNOPHARMACOLOGICAL RELEVANCE: Rubus idaeus Linnaeus (RI) is a Chinese herbal medicine that has been widely used in China for a long time to reinforce the kidney, nourish the liver, improve vision, and arrest polyuria. AIM OF THE STUDY: This work aims to evaluate the recent progress of the chemical composition, pharmacological activity, pharmacokinetics, metabolism, and quality control and of Rubus idaeus, which focuses on the insufficiency of existing research and will shed light on future studies of Rubus idaeus. METHODS: Literatures about "Rubus idaeus","Red raspberry" and "Fupenzi"are retrieved by browsing the database, such as Web of Science (http://www.webofknowledge.com/wos), Pubmed (https://pubmed.ncbi.nlm.nih.gov/), CNKI (http://www.cnki.net/), and Wanfang Data (http://www.wanfangdata.com.cn). In addition, related textbooks and digital documents are interrogated to provide a holistic and critical review of the topic. The period of the literature covered from 1981 to 2022. RESULTS: Approximately 194 compounds have been isolated from Rubus idaeus, which is rich in phenols, terpenoids, alkaloids, steroids, and fatty acids. Numerous investigations have demonstrated that Rubus idaeus exhibits many pharmacological activities, including hypoglycemic and hypolipidemic, anti-Alzheimer effect, anti-osteoporosis, hepatoprotective, anti-cancer, neuroprotective, anti-bacteria and skin care, etc. However, it is worth noting that most of the research is not associated with the conventional effect, such as reducing urination and treating opacity of the cornea. CONCLUSION: The effectiveness of Rubus idaeus has been proved by its long-term clinical application. The research on the pharmacological activity of Rubus idaeus has flourished. In many pharmacological experiments, only the high-dose group can achieve the corresponding efficacy, so the efficacy of Rubus idaeus needs to be further interrogated. Meanwhile, the relationship between pharmacological activity and specific compounds of Rubus idaeus has not been clarified yet. Last but not least, studies involving toxicology and pharmacokinetics are very limited. Knowledge of bioavailability and toxicological behavior of Rubus idaeus can help understand the herb's pharmacodynamic and safety profile.

Activation of caspase-3 in gastric adenocarcinoma AGS cells by Xylopia aethiopica (Dunal) A. Rich. fruit and characterization of its phenolic fingerprint by HPLC-DAD-ESI(Ion Trap)-MSn and UPLC-ESI-QTOF-MS2.

While the fruits of Xylopia aethiopica (Dunal) A. Rich. are important in African countries as a local trade product, their composition remains scarcely investigated. Phenolic fingerprint is herein delivered through HPLC-DAD-ESI(Ion Trap)-MSn and UPLC-ESI-QTOF-MS2 analysis, six cinnamoylquinic acid derivatives and twenty-four flavonoid glycosides being determined, chrysoeriol-7-O-glycosides being the main constituents. A cytotoxicity screening of twenty-eight hydroethanol extracts, obtained from a collection of Guinea-Bissauan plants, against A549 and AGS carcinoma cells, revealed the selective and potent effect towards AGS cells (IC50 = 151 × 10-3 g L-1), upon exposure to the extract from X. aethiopica fruits. Additional experiments demonstrated insignificant effect on LDH release at 151 × 10-3 g L-1, morphological analysis further suggesting induction of apoptosis. Pro-apoptotic effects were confirmed, as the extract enabled the activation of the effector caspase-3, broadening the knowledge on the anticancer mechanisms elicited by the fruits of X. aethiopica. Phenolic constituents might contribute to the cytotoxic effects, particularly via caspase-3 activation. Considering that X. aethiopica fruit is very often referred as an anticancer ingredient in Africa, but mainly the potent cytotoxicity herein recorded, our results call for additional research aiming to identify non-phenolic constituents contributing to the effects and also to further detail the anticancer mechanisms.

A kaempferol-3-O-ß-d-glucoside, intervention effect of astragalin on estradiol metabolism.

Kaempherol-3-O-ß-d-glucoside, known as astragalin, is one of flavonoids found in a variety of plants including Cuscuta australis R.Br. In recent studies, astragalin possess many biological functions. Although astragalin is formed by linking glucose to kaempherol, its biological activity is not the same as kaempferol. In vivo, 17 ß-estradiol (E2) is hydroxylated by cytochrome P450 (CYP) 1B1 to form 4-hydroxy-E2 (4-OH-E2). This metabolite 4-OH-E2 is highly expressed in tumor tissues and has a strong tumorigenic effect. In this paper, the inhibition of astragalin and kaempferol on the activity of cytochrome 1B1 catalyzing estradiol to form 4-hydroxy-estradiol was studied, and the structure-activity relationship between astragalin and kaempferol due to their structural differences was discussed. This study showed that astragalin could inhibit the activity of CYP1B1. The inhibitory effect of astragalin (IC50 5.36 ±â€¯1.13 µM) was weaker than kaempferol (IC50 0.45 ±â€¯0.11 µM). For astragalin, Ki and Vmax values were 4.061 ±â€¯0.737 µM and 1.457 pmol/µg protein/min, while for kaempferol, Ki and Vmax values were 2.631 ±â€¯0.381 µM protein/min and 1.023 ±â€¯0.231 pmol/µg. By kinetic analysis, astragalin and kaempferol were all mixed inhibition, indicating that although astragalin is formed by linking glucose to kaempherol, its inhibitory mechanism on CYP1B1 remained unchanged, and still belonged to a mixed inhibition. The data indicated that astragalin has been able to inhibit the metabolism of estradiol into the carcinogenic metabolite 4-hydroxyl-estradiol in vivo and illustrated an anti-tumor mechanism of astragalin. This study helps to reveal the structure-activity relationship between CYP1B1 activity and its inhibitors.

Cycloartane-type triterpenoid derivatives and a flavonoid glycoside from the burs of Castanea crenata.

Five undescribed cycloartane-type triterpenoids, which were isolated for the first time from the genus, and a flavonoid glycoside together with 11 known compounds were isolated from the burs of Castanea crenata. The structures were elucidated based on the spectroscopic analysis of 1D and 2D NMR and MS data. All isolated compounds were evaluated for antiviral activities against HRV1B-, CVB3-, and PR8-infected cells. Most kaempferol derivatives showed statistically significant antiviral activities against HRV1B-infected cells. Among the tested compounds, kaempferol-3-O-[2″,6″-di-O-Z-p-coumaroyl]-ß-d-glucopyranoside exhibited the most consistent and effective antiviral activities against all infections.

Bioguided extraction of phenolic compounds and UHPLC-ESI-Q-TOF-MS/MS characterization of extracts of Moringa oleifera leaves collected in Brazil.

Moringa oleifera leaves are used in Brazilian folk medicine for their hypoglycemic and nutritional properties. In this context, the chemical and biological characteristics were determined. Conventional successive solid-liquid extraction with simultaneous bioguided purification using solvents with different polarities was performed with M. oleifera leaves, yielding six fractions and extracts. The fractions showed better results for antioxidant activity than the extracts. All of them were evaluated by scavenging of synthetic free radicals and reactive oxygen species, and Fr-Ace and Fr-EtOAc showed >100 mg GAE g-1 of phenolic content, while for FRAP and ORAC assays the values were higher than 1600 µmol Fe2+ g-1 and 3500 mmol TEAC g-1 respectively. The UPLC-ESI-QTOF-MS analysis of hydroalcoholic extract (HE) allowed identifying 24 compounds, with flavonoid derivatives being the most abundant group. Furthermore, the alkaloid trigonelline and sesquiterpenoid abscisic acid were identified for the first time in M. oleifera leaves. Finally, gallic acid, caffeic acid, rutin and quercetin were found in concentrations of 16.5, 2129, 477.4 and 127.5 µg g-1 respectively in HE, all of which were higher in fractions and extracts. These results suggest that bioguided extraction is an important technique, due to its ability to concentrate active compounds in a logical and rational way. In addition, M. oleifera leaves grown in Brazil are an important source of phenolic compounds with antioxidant activity that can be used in food, nutraceutical and pharmaceutical products.

Chemodiversity of two closely related tetraploid Centaurium species and their hexaploid hybrid: Metabolomic search for high-resolution taxonomic classifiers.

Species within the genus Centaurium readily hybridize and polyploid complexes are often seen in natural populations. We describe phytochemical profiles of newly discovered allohexaploid hybrid, here named Centaurium pannonicum, and its parental tetraploid species C. erythraea and rare C. littorale ssp. compressum. Our aim was to examine chemodiversity of these taxa in the area of Vojvodina (North Serbia) and to perform metabolomics search for chemical classifiers which would provide high resolution discrimination of parental and hybrid individuals. In sum, UHPLC-MS/MS Orbitrap metabolomics fingerprinting revealed seventy compounds in methanol extracts. Despite the lack of qualitative chemical novelty in hybrid plants, UHPLC-qqqMS targeted metabolomics approach, aimed at three secoiridoid compounds and seventeen phenolics, pointed to considerable differences in quantitative composition of these dominant compounds among the plant taxa studied. In addition to the difference in the ploidy levels, the hybrid taxon was well distinguished from both parental species based on metabolite profiles, and, for most individuals, positioned intermediately to the parental taxa in both PCA and hierarchical clustering. After optimizing and comparing several statistical learning methods, it was possible to narrow the number of taxonomic classifiers to five (three xanthones, one secoiridoid glycoside, and one phenolic acid), while increasing the differentiation resolution. The presented metabolomics approach will certainly, along with morphometrics and molecular genetics studies, have high impact on further elucidation of complex relationships among taxa within the genus Centaurium.

The flower of Edgeworthia gardneri (wall.) Meisn. suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: The flower of Edgeworthia gardneri (Wall.) Meisn., locally named "Lvluohua, ", has been widely used as Tibetan folk medicine for the treatment of metabolic diseases for a long time. AIM OF THIS STUDY: To evaluate the anti-adipogenesis effect of ethyl acetate extract of the flower of E. gardneri (EEG extract) in 3T3-L1 adipocytes. MATERIALS AND METHODS: Obesity-related parameters such as lipid accumulation and TG content were determined by Oil red O staining and enzymatic kit, respectively. Western blotting was used to determine the expressions of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein-α (C/EBPα), phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). Moreover, main constituents of EEG extract were analyzed by high performance liquid chromatography (HPLC). RESULTS: EEG extract decreased the lipid and triglyceride (TG) accumulations during the differentiation process and down-regulated the adipogenesis-related transcriptional factors PPARγ and C/EBPα. EEG extract treatment increased AMPK and ACC phosphorylation. In addition, pretreatment with AMPK inhibitor, weakened the inhibitory effects of EEG extract on the expressions of PPARγand C/EBPα. HPLC analysis indicated that tiliroside was the main constituent in EEG extract. CONCLUSIONS: These results suggest that EEG extract may exert anti-adipogenic effects through modulation of the AMPK signaling pathway.

Anti-osteoporosis effect of Epimedium via an estrogen-like mechanism based on a system-level approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium is a popular traditional herbal medicine worldwide that has long been used to relieve osteoporosis. The estrogenic properties of the herb are conferred by several phytoestrogens, such as flavonoids, lignans, and steroids. However, the poor understanding on the estrogen-like mechanism of Epimedium at the molecular and system levels limits the applications of this herb in osteoporosis treatment. MATERIALS AND METHODS: In this study, systems pharmacology was established to investigate the relationship between Epimedium and estrogen against osteoporosis by integrating active component screening, drug-likeness evaluation, herb feature mapping, target prediction and validation, and network analysis. RESULTS: A total of 77 active components that possessed similar structural features to estrogen as determined using herb feature mapping were selected from Epimedium by oral bioavailability prediction and drug-likeness evaluation. Twenty three osteoporosis-related targets were obtained from the active components of Epimedium as potential targets, 11 of which were common targets with estrogen. All osteoporosis-related targets were further mapped to compound-target and target-pathway networks. Results displayed that Epimedium can exert anti-osteoporosis effects by directly regulating the 11 estrogen-related targets and a set of target proteins on five estrogen-related pathways. CONCLUSION: This study explained the estrogen-like mechanism of Epimedium in preventing and treating osteoporosis, and provided a new standpoint for exploring the traditional herbal medicine against osteoporosis.

Identification and quantification of glucosinolate and flavonol compounds in rocket salad (Eruca sativa, Eruca vesicaria and Diplotaxis tenuifolia) by LC-MS: highlighting the potential for improving nutritional value of rocket crops.

Liquid chromatography mass spectrometry (LC-MS) was used to obtain glucosinolate and flavonol content for 35 rocket accessions and commercial varieties. 13 glucosinolates and 11 flavonol compounds were identified. Semi-quantitative methods were used to estimate concentrations of both groups of compounds. Minor glucosinolate composition was found to be different between accessions; concentrations varied significantly. Flavonols showed differentiation between genera, with Diplotaxis accumulating quercetin glucosides and Eruca accumulating kaempferol glucosides. Several compounds were detected in each genus that have only previously been reported in the other. We highlight how knowledge of phytochemical content and concentration can be used to breed new, nutritionally superior varieties. We also demonstrate the effects of controlled environment conditions on the accumulations of glucosinolates and flavonols and explore the reasons for differences with previous studies. We stress the importance of consistent experimental design between research groups to effectively compare and contrast results.

Changes of major tea polyphenols and production of four new B-ring fission metabolites of catechins from post-fermented Jing-Wei Fu brick tea.

HPLC analysis of samples from four major fermentation procedures of Jing-Wei Fu brick tea showed that the level of major tea catechins epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) dropped increasingly to about 1/3 in the final product. Phytochemical study of the final product led to the discovery of four new B-ring fission metabolites of catechins (BRFCs) Fuzhuanin C-F (1-4) together with three known BRFCs (5-7), six known catechins (8-13), five simple phenols (14-18), seven flavones and flavone glycosides (19-25), two alkaloids (26, 27), three triterpenoids (28-30) and one steroid (31). The structures were elucidated by spectroscopic methods including 1D and 2D NMR, LC-HR-ESI-MS, IR, and CD spectra. Five compounds (16-18, 28, 29) were reported for the first time in tea. Possible pathways for the degradation of major tea catechins and the generation of BRFCs were also provided.

Cuscuta chinensis Lam.: A systematic review on ethnopharmacology, phytochemistry and pharmacology of an important traditional herbal medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta chinensis Lam. has found its use as a traditional medicine in China, Korea, Pakistan, Vietnam, India and Thailand. It is commonly used as an anti-aging agent, anti-inflammatory agent, pain reliever and aphrodisiac. To provide an overview of the ethnopharmacology, phytochemistry, pharmacokinetics, pharmacology and clinical applications of Cuscuta chinensis, as well as being an evidence base for further research works of the plant. MATERIALS AND METHODS: The present review covers the literature available from 1985 to 2014. The information was collected from journals, books, theses and electronic search (Google Scholar, PubMed, ScienceDirect, ESBCO, Springerlink and CNKI). Literature abstracts and full-text articles were analyzed and included in the review. RESULTS: Many phytochemicals have been isolated, identified and published to date, including: at least 18 flavonoids; 13 phenolic acids; 2 steroids; 1 hydroquinone; 10 volatile oils; 22 lignans; 9 polysaccharides; 2 resin glycosides; 16 fatty acids. These phytochemicals and plant extracts exhibit a range of pharmacological activities that include hepatoprotective, renoprotective, antiosteoporotic, antioxidant, anti-aging, antimutagenic, antidepressant, improve sexual function, abortifacient effects, etc. CONCLUSION: This present review offers primary information for further studies of Cuscuta chinensis. The in vitro studies and in vivo models have provided a bioscientific explanation for its various ethnopharmacological uses and pharmacological activities (most notably antioxidant effects) especially in the prevention of hepatic disease and renal failure. It is necessary and important to do more pharmacokinetic and toxicological research works on human subjects in order to inform the possible active compounds in the body and validate its safety in clinical uses.

Chemical constituents of Morus alba L. and their inhibitory effect on 3T3-L1 preadipocyte proliferation and differentiation.

Mulberry leaf, an important traditional Chinese medicine, possesses many biological activities, including effects of anti-obesity. However, which constituents of mulberry leaf are responsible for its anti-adipogenic action is unclear. This study primarily investigated the chemical constituents from mulberry leaf and their bioactivity on the proliferation and differentiation of 3T3-L1 preadipocytes. A new flavane derivative, (2S)-4'-hydroxy-7-methoxy-8-prenylflavan (1), together with twelve known compounds including three flavanes (2-4), three chalcones (5-7), two flavones (8-9), two benzofurans (10-11) and two coumarin (12-13) was isolated from mulberry leaf. The structure of the new compound was elucidated by various spectroscopic methods including UV, HR-ESI-MS, (1)H and (13)C NMR and CD. The results of activity screening showed that compound 2, 6 and 7 inhibited the proliferation and differentiation of 3T3-L1 preadipocytes.