Potential Anti-Alzheimer Properties of Mogrosides in Vitamin B12-Deficient Caenorhabditis elegans.

Vitamin B12 deficiency can lead to oxidative stress, which is known to be involved in neurodegenerative diseases such as Alzheimer's disease (AD). Mogrosides are plant-derived triterpene glycosides that exhibit anti-inflammatory and antioxidant activity in animal cell lines and mouse models. Since amyloid-ß toxicity is known to cause oxidative stress and damage to brain cells, we hypothesized that mogrosides may have a protective effect against AD. In this study, we investigated the potential anti-AD effect of mogrosides in vitamin B12-deficient wild-type N2 and in transgenic CL2355 Caenorhabditis elegans expressing amyloid-ß peptide. Our data indicated that mogrosides have a beneficial effect on the lifespan and egg-laying rate of N2 and vitamin B12-deficient N2 worms. Additionally, the results revealed that mogrosides can effectively delay the paralysis of CL2355 worms as determined by serotonin sensitivity assay. Our analysis showed that mogrosides increase the expression of oxidative protective genes in N2 worms fed with vitamin B12-deficient OP50 bacterium. We conclude that mogrosides may exert preventative rather than curative effects that counteract the detrimental vitamin B12-deficient environment in N2 and CL2355 C. elegans by modulating oxidation-related gene expression.

Dulong People's Traditional Knowledge of Caryota obtusa (Arecaceae): a Potential Starch Plant with Emphasis on Its Starch Properties and Distribution Prediction.

The greatest global challenge is to ensure that all people have access to adequate and nutritious food. Wild edible plants, particularly those that provide substitutes for staple foods, can play a key role in enhancing food security and maintaining a balanced diet in rural communities. We used ethnobotanical methods to investigate traditional knowledge on Caryota obtusa, a substitute staple food plant of the Dulong people in Northwest Yunnan, China. The chemical composition, morphological properties, functional, and pasting properties of C. obtusa starch were evaluated. We used MaxEnt modeling to predict the potential geographical distribution of C. obtusa in Asia. Results revealed that C. obtusa is a vital starch species with cultural significance in the Dulong community. There are large areas suitable for C. obtusa in southern China, northern Myanmar, southwestern India, eastern Vietnam, and other places. As a potential starch crop, C. obtusa could substantially contribute to local food security and bring economic benefit. In the future, it is necessary to study the breeding and cultivation of C. obtusa, as well as the processing and development of starch, to solve long-term and hidden hunger in rural areas.

[Two pairs of phloroglucinol enantiomers from Hypericum wightianum and their stereochemical structures].

The chemical constituents in the ethanol extract of Hypericum wightianum(Hypericaceae) were purified by column chromatography and identified via magnetic resonance imaging(NMR), high-resolution mass spectrum, and circular dichroism. A total of 22 compounds were identified, including eight polyprenylated phloroglucinols(1-8), three chromones(9-11), and three terpenoids(14-16) and so on. Among them, compounds 16 and 17 were first reported in the genus Hypericum, and compounds 1-11, 14, 15, and 19 were first isolated from H. wightianum. Compounds 1-4 were previously reported as two pairs of enantiomers. This study reported the chiral resolutions and absolute configurations of compounds 1-4 for the first time.

A Caffeic Acid Matrix Improves In Situ Detection and Imaging of Proteins with High Molecular Weight Close to 200,000 Da in Tissues by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

To our knowledge, this was the first study in which caffeic acid (CA) was successfully evaluated as a matrix to enhance the in situ detection and imaging of endogenous proteins in three biological tissue sections (i.e., a rat brain and Capparis masaikai and germinating soybean seeds) by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Our results show several properties of CA, including strong ultraviolet absorption, a super-wide MS detection mass range close to 200,000 Da, micrometer-sized matrix crystals, uniform matrix deposition, and high ionization efficiency. More high-molecular-weight (HMW) protein ion signals (m/z > 30,000) could be clearly detected in biological tissues with the use of CA, compared to two commonly used MALDI matrices, i.e., sinapinic acid (SA) and ferulic acid (FA). Notably, CA shows excellent performance for HMW protein in situ detection from biological tissues in the mass range m/z > 80,000, compared to the use of SA and FA. Furthermore, the use of a CA matrix also significantly enhanced the imaging of proteins on the surface of selected biological tissue sections. Three HMW protein ion signals (m/z 50,419, m/z 65,874, and m/z 191,872) from a rat brain, two sweet proteins (mabinlin-2 and mabinlin-4) from a Capparis masaikai seed, and three HMW protein ion signals (m/z 94,838, m/z 134,204, and m/z 198,738) from a germinating soybean seed were successfully imaged for the first time. Our study proves that CA has the potential to become a standard organic acid matrix for enhanced tissue imaging of HMW proteins by MALDI-MSI in both animal and plant tissues.

[Traditional medicinal knowledge in Lancang-Mekong River:a case study in Lancang Lahu autonomous county].

Lancang Lahu autonomous county, where the Lancang-Mekong River flows by, was selected as the case site to investigate the traditional medicinal knowledge(TMK). A comparison of TMK between Lancang county and other places in the Lancang-Mekong sub-region was conducted. Research on TMK has been seldom reported although there are abundant medicinal resources in this sub-region. The key informant interview and other methods have been adopted in the field surveys in the past six years. The investigation revealed that there was rich TMK and various herbal medicine resources in Lancang county. A total of 220 folk prescriptions have been collected, which were normally simple with easy processing methods and usages, and most raw materials were freshly used. As for medicinal plants, 121 species in 67 families have been documented. Other findings included that TMK in Lancang county was remained at the level of medication based on experience only. The processing methods of herbal medicines were simple and the bioactive ingredients were not clear. Without text and cultural support for self-teaching, coupled with conservative inheritance, it resulted in massive losses of TMK. The folk doctors have accumulated their factions based on self-study or ancestral experience. There was different treatment experience among folk doctors, but the safety and effectiveness should be paid attention to. The folk doctors used various herbal medicines, but there was a lack of standards or specifications for quality control. Given the problems existing in inheritance and development, conservation strategies were proposed in the present study.

Cytotoxic Xanthones from Hypericum stellatum, an Ethnomedicine in Southwest China.

Hypericum stellatum, a species endemic to China, is used to treat hepatitis by several ethnic groups in Guizhou Province. This research was inspired by the traditional medicinal usage of H. stellatum, and aims to explore the phytochemistry and bioactivity of H. stellatum to explain why local people in Guizhou widely apply H. stellatum for liver protection. In this study, two new prenylated xanthones, hypxanthones A (8) and B (9), together with seven known compounds, were isolated from the aerial parts of the plant. Spectroscopic data as well as experimental and calculated ECD spectra were used to establish the structures of these compounds. Six xanthones isolated in this study, together with four xanthones previously isolated from H. stellatum, were evaluated for their growth-inhibitory activities against five human liver carcinoma cell lines to analyze the bioactivity and structure-activity relationship of xanthones from H. stellatum. Isojacareubin (6) showed significant cytotoxicity against five human liver carcinoma cell lines, with an IC50 value ranging from 1.41 to 11.83 µM, which was stronger than the positive control cisplatin (IC50 = 4.47-20.62 µM). Hypxanthone B (9) showed moderate cytotoxicity to three of the five cell lines. Finally, structure-activity analysis revealed that the prenyl and pyrano substituent groups of these xanthones contributed to their cytotoxicity.

Modified Abietane Diterpenoids from Whole Plants of Selaginella moellendorffii.

A new modified abietane diterpenoid, (3S,4S,5R,10S)-18(4→3)-abeo-3,4,12,18-tetrahydroxy-8,11,13-abietatrien-7-one (1), and two novel dimers, selaginedorffones A (2) and B (3), featuring a new cyclohexene moiety that was biogenetically constructed from two modified abietane diterpenoids through a Diels-Alder reaction were obtained from a methanolic extract of Selaginella moellendorffii, a traditional Chinese herb. The structures of 1-3 were identified by a combination of NMR spectroscopic analysis and ECD calculations. In the present study, diterpenoids were identified from S. moellendorffii for the first time, which supports the presence of diterpene synthases in this plant. These three diterpenoids (1-3) were evaluated for their growth-inhibitory activities against several human cancer cell lines. Of these substances, selaginedorffone B (3) showed cytotoxicity against the MCF-7 human-breast-cancer-cell line (IC50 9.0 µM).

Identification of Potential Biomarkers from Aconitum carmichaelii, a Traditional Chinese Medicine, Using a Metabolomic Approach.

Despite their well-known toxicity, Aconitum species are important traditional medicines worldwide. Aconitum carmichaelii, known in Chinese as (fuzi), is an officially recognized traditional Chinese medicine with characteristic analgesic and anti-inflammatory activities, whose principal pharmacological ingredients are considered as aconitine-type diterpene alkaloids. Notwithstanding the long-recorded use of A. carmichaelii in traditional Chinese medicine, no single-entity aconitum alkaloid drug has been developed for clinical use. UPLC-Q-TOF-MS was used to investigate the marker compounds that can be used to differentiate A. carmichaelii from seven other Aconitum species collected in Yunnan Province. Nontargeted principle component analysis scores plots found that all the tested Aconitum species clustered into three distinct groups, and A. carmichaelii was significantly different chemically than the other seven species. Furthermore, the primary and lateral roots of A. carmichaelii also showed significant differences. Using orthogonal partial least squares discriminate analysis analysis, eight marker compounds were identified, including 14-acetylkarakoline, aconitine, carmichaeline, fuziline, hypaconitine, mesaconitine, neoline, and talatisamine. Four of these aconitum alkaloids, fuziline, hypaconitine, mesaconitine, and neoline, showed significant analgesic activity in a dose-dependent manner compared to the negative and positive controls. However, hypaconitine, mesaconitine, and neoline exhibited significant acute toxicity activity, while fuziline showed no acute toxicity in mice, suggesting the relative safety of this alkaloid. This study provides a good example of how to differentiate an authentic medicinal plant from common adulterants using a metabolomics approach, and to identify compounds that may be developed into new drugs.

New aporphine alkaloids from the aerial parts of Piper semiimmersum §.

Two new aporphine alkaloids, semiimmersumines A (1) and B (2), along with 20 known compounds, were isolated from the aerial parts of Piper semiimmersum (Piperaceae). The structures of the new compounds were elucidated based on the analysis of 1D and 2D NMR, MS, and CD data. The absolute configuration of semiimmersumine A (1) was determined by single crystal X-ray diffraction analysis using anomalous dispersion with copper radiation. The effects of all compounds from the plant on rabbit platelet aggregation induced by thrombin (IIa) or PAF were also evaluated.

[Chemical constituents of Hypericum stellatum and their antioxidant bioactivities].

Hypericum stellatum is an important ethnomedicinal plant endemic to southwest China. Ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was applied to analyze the chemical constituents of H. stellatum. Seventeen compounds from H. stellatum were tentatively identified using UPLC-Q-TOF-MS data. Antioxidant activity and total phenolic content were investigated by DPPH assay and Folin-Ciocalted methods. The EtOAc extract with high total phenolic content showed prominent antioxidant activity. The EtOAc extract of H. stellatum was separated and purified by column chromatography, including silica gel, Sephedex LH-20, and RP-HPLC. The isolates were defined by 1D, 2D NMR data. As a result, ten compounds were isolated and assigned as quercetin (Ⅰ), quercetin 3-O-ß-D-glucopyranoside (Ⅱ), 1,3,6,7-tetrahydroxylxanthone (Ⅲ), 1,3,5,6-tetrahydroxyxanthone (Ⅳ), 1,3,7-trihydroxyxanthone (Ⅴ), 3, 6, 7-trihydroxy-1-methoxyxanthone (Ⅵ), calycinoxanthon D (Ⅶ), caffeic acid ethyl ester (Ⅷ), chlorogenic acid (Ⅸ) and chlorogenic acid ethyl ester (Ⅹ). This is the first report on chemical constituents and bioactivity of H. stellatum. The antioxidant activity of chemical constituents was tentatively found, which provided a foundation for further researches on the genus Hypericum and the traditional uses of H. stellatum.

[Studies on volatile oils compounds of Acorus macrospadiceus based on GC-MS, an ethnomedicinal and food plant used by local people in southwest China].

Acorus macrospadiceus is a common medicinal and food plant used different ethnic groups in Guizhou and surrounding areas. In this paper, the leaf and rhizome tissues of A. macrospadiceus were hydro-distilled to extract the volatile oils. The chemical constituents of these oils were analyzed by GC-MS and identified using the NIST 14.0 & NIST 14.0s mass spectral libraries. The relative contents of chemical constituents from the different plant parts were determined by area normalization. The analysis of A. macrospadiceus volatile oils resulted in the identification of 25 compounds from the leaf and 36 compounds from the rhizome. The identified compounds accounted for 97.85% of the leaf essential oil content and 97.18% of the rhizome essential oil content. The main volatile constituent of A. macrospadiceus was identified as estragole (93.56% of total oil content in leaf and 71.62% of total oil content in rhizome). Fourteen compounds were found to be common to essential oils of both leaf and rhizome. However, the relative amounts of these compounds were significantly different between the plant parts; the remaining identified compounds were unique to each part. This comparison of volatile oils from the different parts of A. macrospadiceus can serve as a reference for future development. Because of the higher estragole content and better harvesting sustainability of the leaves compared to rhizomes, the leaves of A. macrospadiceus deserve consideration for sustainable development. However, when we use it as a medical plant, we should draw a distinction between it with A. tatarinowii.

UPLC-QTOFMS(E)-Guided Dereplication of the Endangered Chinese Species Garcinia paucinervis to Identify Additional Benzophenone Derivatives.

A number of Garcinia species accumulate benzophenone derivatives that may be useful for the treatment of breast cancer. The dereplication of new benzophenone derivatives from Garcinia species is challenging due to the occurrence of multiple isomers and the known compounds found in their extracts. In the current study, a strategy is described using the UPLC-QTOFMS(E) technique to identify tentatively the known and uncharacterized benzophenones of interest based upon the characteristic fragmentation ions. Several UPLC-QTOFMS peaks (a-ee) appeared to contain benzophenone derivatives, and 12 of these peaks contained compounds with MS ionization profiles not consistent with previously identified compounds from the seeds of Garcinia paucinervis, an endangered Chinese species. The targeted isolation of unidentified compounds of interest afforded five new benzophenones, paucinones E-I (1-5), which were determined by MS and NMR analysis and ECD spectroscopy. These compounds were evaluated for cytotoxicity against three breast cancer cell lines inclusive of MDA-MB-231, SKBR3, and MCF-7. These results indicate that the UPLC-QTOFMS(E)-guided isolation procedure is an efficient strategy for isolating new benzophenones from Garcinia species.

Structural diversity and bioactivities of natural benzophenones.

Natural benzophenones are a class of compounds consisting of more than 300 members, which exhibit great structural diversity and bioactive properties. Many benzophenones have been reported from higher plants or fungi, most with polyisoprenylated benzophenone skeletons, and are mainly found in the Clusiaceae (formerly Guttiferae) family, a number from edible or medicinal species. Owing to their variable substituents and complex ring systems, many new polyisoprenylated benzophenones (PPBS), including ones with unusual skeletons, were isolated and identified. These natural benzophenones exhibit a range of biological activities including antifungal, anti-HIV, antimicrobial, antioxidant, antiviral and cytotoxic. Because of the increased numbers and biological importance of these unique natural product polyphenols, we will review natural benzophenones and provide an in-depth discussion of their structural diversity and biological activity. By focusing on these key developments in benzophenones, we will contribute a focused review, selecting examples mostly from the last 15 years, but extending our scope to other historically important benzophenones discovered prior to that time.

Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues.

Twenty-five amide alkaloids (1-25) from Piper boehmeriifolium and 10 synthetic amide alkaloid derivatives (39-48) were evaluated for antiproliferative activity against eight human tumor cell lines, including chemosensitive and multidrug-resistant (MDR) cell lines. The results suggested tumor type-selectivity. 1-[7-(3,4,5-Trimethoxyphenyl)heptanoyl]piperidine (46) exhibited the best inhibitory activity (IC50=4.94 µM) against the P-glycoprotein (P-gp)-overexpressing KBvin MDR sub-line, while it and all other tested compounds, except 9, were inactive (IC50 >40 µM) against MDA-MB-231 and SK-BR-3. Structure-activity relationships (SARs) indicated that (i) 3,4,5-trimethoxy phenyl substitution is critical for selectivity against KBvin, (ii) the 4-methoxy group in this pattern is crucial for antiproliferative activity, (iii) double bonds in the side chain are not needed for activity, and (iv), in arylalkenylacyl amide alkaloids, replacement of an isobutylamino group with pyrrolidin-1-yl or piperidin-1-yl significantly improved activity. Further study on Piper amides is warranted, particularly whether side chain length affects the ability to overcome the MDR cancer phenotype.

Indole alkaloid glycosides from the aerial parts of Strobilanthes cusia.

Three indole alkaloid glycosides, strobilanthosides A-C (1-3), two known indole alkaloid glucosides (4 and 5), and five phenylethanoid glycosides (8-10) were isolated from the aerial parts of Strobilanthes cusia. The structures of the new compounds were elucidated by spectrometric analysis, and the absolute configurations of 1 and 2 were established by ECD spectrocsopy. N'-ß-d-Glucopyranosylindirubin (5) showed weak antibacterial activity (MIC 62.5-125 µM) against Staphylococcus aureus.

Prospecting for bioactive constituents from traditional medicinal plants through ethnobotanical approaches.

Pharmacologically active constituents from traditional medicinal plants have received great attention as sources of novel agents, pharmaceutical intermediates, and chemical entities for synthetic or semisynthetic drugs due to their potent pharmacological activities, low toxicity, and economic viability. Numerous components have been isolated from traditional medicinal plants, including alkaloids, flavonoids, and terpenoids, and clinical and experimental studies suggested that these components have useful pharmacological properties such as antiinfectious, antioxidative, and antiinflammatory effects. In this review, modern ethnobotanical approaches to explore folk medicinal plants as candidates for drug discovery with the greatest possibility of success are discussed. Determining the bioactive mechanisms and tracing structure-activity relationships will promote the discovery of new drugs and pharmacological agents.

Ethnobotanical uses, phytochemistry and bioactivities of Cymbopogon plants: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon (Poaceae) plants have been used for various purposes by many indigenous peoples in all continents. In particular, almost all species in the genus have traditionally been used as folk medicine to treat ailments. Traditional application records indicated that Cymbopogon might be used extensively to treat cold, dizziness, headache, loss of appetite, abdominal pain, rheumatism, diarrhea, whole grass for cold, sore throat, tracheitis and others. AIMS OF THE REVIEW: Despite several research confirmed that Cymbopogon includes a range of active components, no review has been undertaken to consolidate information on its traditional uses, phytochemistry, pharmacology, and/or quality control. Thus this article aims to update a comprehensive review about the traditional uses, phytochemistry, pharmacology, cultivation techniques, economic benefits, trade, threats, and future conservation implications of Cymbopogon species. It may provide informative data for future development and further investigation of this important plant group. MATERIALS AND METHODS: Traditional medicinal books and ethnomedicinal publications related to Cymbopogon from 1992 to 2023 were collated to investigate its ethnobotanical, phytochemical and pharmacological information. The online databases including Google Scholar, SciFinder, Web of Science, Scopus, Springer Link, PubMed, Wiley, China National Knowledge Infrastructure (CNKI), Baidu Scholar, and WanFang Database were screened. RESULTS: Cymbopogon (Gramineae or Poaceae) plants have been grown worldwide. Traditional Chinese medicine and other medicinal systems believes that Cymbopogon has the effect of relieve a cough, analgesia, treating dizziness, traumatic injury and can relieve abdominal pain. A total of 153 compounds, including flavonoids, terpenoids, fatty acid and other compounds were isolated or identified from Cymbopogon species by phytochemical studies. The extracts or compounds from Cymbopogon have exhibited numerous biological activities such as antibacterial, antiinflammatory, antiviral, antineoplastic, antiarrhythmic, antidiabetic and other activities. The rich contents of citronellal, citronellol and geraniol found in Cymbopogon also provide significant nutritional benefits. CONCLUSION: Based on their traditional uses, phytochemicals, and pharmacological activities, Cymbopogon plants are potential medicinal and edible resources with diverse pharmacological effects. Due to various advantages of this group, they possess huge application potential in food and pharmaceutical industries, and animal husbandry. Among them, citronella is very important in terms of economic development. Further comprehensive research to evaluate the medicinal properties of Cymbopogon species will be necessary for future development.

Traditional uses, phytochemistry, pharmacology, toxicity and clinical application of traditional Chinese medicine Cynoglossum amabile: a review.

Cynoglossum amabile, a member of the Boraginaceae family, is a well-known traditional Chinese medicine and ethnomedicine known as Daotihu. Despite several studies confirming the presence of bioactive pyrrolizidine alkaloids such as amabiline, ambelline, echinatine, europine, and others in C. amabile, there has been no comprehensive review of its traditional uses, phytochemistry, and pharmacology thus far. This review was conducted by thoroughly examining the literature and analyzing network databases. It covers various aspects of C. amabile, including botanical characteristics, geographical distribution, traditional applications, phytochemistry, pharmacological activities, toxicology, and clinical applications. The results have shown that C. amabile has been traditionally used for medicinal, edible, and ornamental purposes in China for many centuries. The whole plant, root, and leaf of C. amabile are used by different ethnic groups, such as Lisu, Bai, Naxi, Yi, Jinuo, and Han, to treat malaria, hepatitis, dysentery, leucorrhea, tuberculosis cough, fracture, joint dislocation, trauma bleeding, and skin carbuncle abscess. A total of 47 chemical components, including alkaloids (pyrrolizidine alkaloids, PAs), sterols, organic acids, and saccharides, were isolated from C. amabile. Pharmacological studies show that the chemical extracts of C. amabile possess various biological activities, such as anti-inflammatory, anti-tumor, anti-microbial, cardiovascular effects, ganglionic action, and acetylcholinesterase inhibition. However, it is important to note that C. amabile exhibits hepatotoxicity, with its toxicity being linked to its primary PAs components. Although preliminary studies suggest potential applications in the treatment of prostate diseases and alopecia, further research is needed to validate these clinical uses. Our review highlights the traditional uses, phytochemistry, biological activity, toxicity, and clinical applications of C. amabile. It emphasizes the essential guiding role of the indigenous medicinal knowledge system in developing new drugs. Previous studies have shown that the phytochemical and pharmacological characteristics of C. amabile are significantly related to its traditional medicinal practices. Cynoglossum amabile has excellent market potential and can be further analyzed in terms of phytochemistry, pharmacology, and toxicology, which are critical for its clinical drug safety, quality evaluation, and resource development.

Study on medicinal food plants in the Gaoligongshan Biosphere Reserve, the richest biocultural diversity center in China.

BACKGROUND: Traditional knowledge associated with medicinal food plants (MFPs) plays a vital role in fighting hidden hunger and safeguarding the health of local people. MFPs resources are abundant in the Gaoligongshan area, a biosphere reserve with the richest biocultural diversity in China. Local people of different linguistic groups also have rich traditional botanical knowledge. However, there are still few comprehensive and systematic studies on MFPs there. METHODS: Ethnobotanical investigation including market survey, semi-structured interviews, free listing and key informant interviews was conducted in the Gaoligongshan area, Western Yunnan, Southwest China. A total of 13 local farmers' markets were selected and information about medicinal food plants, including food categories, medicinal and edible parts, modes of consumption, medicinal effects, and distribution were collected. The relative occurrence frequency (RFO) and cultural food significance index (CFSI) were calculated to identify the culturally significant MFPs. RESULTS: A total of 184 species of MFPs, belonging to 83 families, were collected in the Gaoligongshan area, including vegetables (77), medicinal diets (26), fruits (25), spices (18), herbal tea (13), tea substitutes (11), substitutes for staple food (8), nuts (5), oils and fats (4), and dye material (1). The most frequently used families were Fabaceae, Asteraceae and Apiaceae, with 11, 10, and 9 species, respectively. The most frequently used plant parts were the stems, followed by fruits and leaves. Based on the evaluation results of the CFSI and RFO indices, 18 species of MFPs with magnificent local cultural importance have been screened out, such as Houttuynia cordata, Eryngium foetidum, Sechium edule, Centella asiatica and Pseudocydonia sinensis. CONCLUSION: These findings have guiding significance for conservation of traditional knowledge associated with MFPs and facilitation of scientific utilization of MFPs to meet local people's needs for a healthy life.

Metabolomic and chemometric analyses of St. John's wort and related Asian Hypericum species linked to bioactivity.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants in the genus Hypericum (Hypericaceae), include more than 500 species worldwide, and many are valued for their medicinal properties, and are used as traditional herbal medicines. However, only H. perforatum is officially recognized as herbal drug in several pharmacopoeias, and used as an antidepressant clinically. Hypericum perforatum had been used as an herbal medicine since the Han Dynasty (206 B.C. -220 A.D.) in China. It taxonomically belongs to the section Hypericum in the genus Hypericum. There are about 42 species in the section Hypericum, with six species occurring in China. All six are recorded as traditional herbal medicines for treating aliments, including hepatitis, malaria, traumatic hemorrhage, irregular menstruation, wounds, and bruises. AIM OF THE STUDY: The study aimed to characterize the chemical profiles of five phylogenetically related Hypericum species, and compare their metabolites with three H. perforatum products. Informed by ethnobotanical use, the extracts prepared from the five species were further investigated into anticancer, anti-inflammatory and antiplasmodial activity. This study tested the hypothesis that systematic metabolomic and bioactivity characterization of species in section Hypericum will help to validate their phytotherapeutic use and reveal potential drug lead compounds. MATERIALS AND METHODS: Targeted and non-targeted metabolic analyses coupled with chemometrics were conducted on H. perforatum and four medicinal species, H. attenuatum, H. enshiense, H. erectum, and H. faberi, native to China from section Hypericum. UPLC-QTOF-MS/MS and UPLC-TQD-MS/MS were used for non-targeted and targeted metabolic analyses, respectively. Cytotoxicity bioassays on four cancer cell lines, anti-inflammation tests and anti-plasmodial activity on Plasmodium falciparum 3D7, selected based on traditional medicinal use, were evaluated on extracts from Hypericum species. Progenesis QI and EZinfo were used for chemometrics analysis to link the chemical profile and bioassay activity to aid in the identification of bioactive compounds. RESULTS: In total, 58 compounds were identified from the five species, including compounds with well-characterized bioactivity. Hypericum attenuatum, H. erectum, and H. perforatum, displayed the highest cytotoxicity, and contain the cytotoxic compounds petiolin A, prolificin A, and hypercohin G, respectively. Hypericum faberi and H. perforatum showed the highest anti-inflammatory activity, with pseudohypericin, quercetin and chlorogenic acid being observed at higher concentrations. Hypericum perforatum and H. erectum showed anti-plasmodial activity, with higher hyperforin and xanthones in these species that may account for the anti-plasmodial activity. CONCLUSIONS: This study characterized the chemical differences among five Hypericum species using metabolomics. These ethnomedically important species were tested for their biological activities in three distinct in vitro assays. The ethnobotanical data were useful for identifying bioactive Hypericum species. Hypericum attenuatum, H. erectum and H. faberi are promising phytotherapeutic species, although they are much less studied than H. perforatum, St. John's wort. Combining ethnobotanical surveys with chemometric analyses and bioactivity screening can greatly enhance the discovery of promising active constituents.