Oligomeric phloroglucinols with hAChE inhibitory and antibacterial activities from tropic Rhodomyrtus tomentosa.

Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (hAChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a, 3b, 4b, and 5a), six new phloroglucinol trimers (6a, 6b, 7a, 7b, 8a, and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a/3b shared a rare C-5' formyl group, whereas 6a/6b possessed a unique C-7' aromatic ring. In addition, 7a/7b and 8a/8b were rare phloroglucinol trimers with a bis-furan and a C-6' hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (hAChE) inhibitory activity with an IC50 value of 1.21 ± 0.16 µM. The molecular docking studies of 3a and 3b in the hAChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 µg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents.

Munronin V with 7/7/6 tricarbocyclic framework from Munronia henryi harms inhibits tau pathology by activating autophagy.

Munronin V (1), isolated from Munronia henryi Harms, is the first example, to the best of our knowledge, of an unprecedented 7/7/6 tricarbocyclic framework featuring an unusual A,B-seco-limonoid ring. The structures of munronin V were established from extensive spectroscopic and electronic circular dichroism (ECD) analyses. The novel A,B-seco with two seven-membered lactones was formed as a result of Baeyer-Villiger oxidation. Compound 1 activated autophagy and inhibited Tau pathology as revealed by flow cytometric analyses, confocal imaging analysis and western blotting, and this effect was mediated by transcription factor EB (TFEB). These findings suggested that 1 might have potential as a compound for combating Alzheimer's disease.

Dimeric benzylisoquinoline alkaloids from Thalictrum delavayi and their biological activities.

A phytochemical investigation of the whole plants of T. delavayi led to the isolation of five new dimeric benzylisoquinoline alkaloids, thalidelavines A-E (1-5), together with six known congeners (6-11). The structures and absolute configurations of new compounds were established based on analyses of spectroscopic data, ECD calculations, and single crystal X-ray crystallography. Thalidelavines A-E (1-5) were structurally complex bisbenzylisoquinoline alkaloids with various configurations. These isolated alkaloids were evaluated for their cytotoxic and immunosuppressive effects. Among them, both 9 and 10 displayed significant cytotoxicities against T98G cell lines with an IC50 value of 2.1 µM, compared with the positive CPT-11 (IC50 = 3.0 µM). In addition, 5-7 showed remarkable immunosuppressive effects. These findings not only enrich the structural diversity of bisbenzylisoquinoline alkaloids, but also provide potential candidates for the further development of the antitumor and immunosuppressive agents.

Phytochemical and Antibacterial Constituents of Edible Globe Amaranth Flower against Pseudomonas aeruginosa.

Globe amaranth flower, the edible inflorescence of Gomphrena globose L., was used to treat dysentery and ulcer as well as other infectious diseases caused by microbes in Southwest China, but its function and bioactive components need experimental support. In this study, phytochemical constituents and antibacterial bioactivity of globe amaranth flower against P. aeruginosa were carried out. As a result, two new (1 and 2) and eleven known (3-11) compounds were isolated, in which compounds 4-7 displayed anti P. aeruginosa bioactivity with the minimum inhibitory concentration (MIC) from 0.008 to 0.256 mg/mL. Furthermore, with aid of the scanning electron microscope (SEM) and a superficial skin infection model in mice, the most potent compound 4 can significantly destroy the structure of bacteria in vitro and restore bacterial infection damage in vivo.

Anti-inflammatory and analgesic monoterpenoid indole alkaloids of Kopsia officinalis.

ETHNOPHARMACOLOGICAL RELEVANCE: "Ya gai", an important part of Dai medical theory, is traditionally recognized as an antidote. Kopsia officinalis Tsiang et P. T. Li is a "Ya gai" related medicine and has been widely used by Dai people for the treatment of pain and inflammation. Previous literature on title species suggested that monoterpenoid indole alkaloids (MIAs) could be its main bioactive components. However, the specific bioactive ingredients for inflammation-related treatment are still unrevealed, which inspired us to conduct a phytochemical and pharmacological investigation related to its traditional use. AIM OF THE STUDY: To support the traditional use of K. officinalis by assessing the anti-inflammatory and analgesic effects of its purified MIAs. MATERIAL AND METHODS: Compounds were isolated and purified from the barks and leaves of K. officinalis using diverse chromatographic methods. The structures were established by means of extensive spectroscopic analyses and quantum computational technique. The anti-inflammatory activities of the purified MIAs were evaluated in vitro based on the suppression of lipopolysaccharide-activated inflammatory mediators (COX-2, IL-1ß, and TNF-α) in RAW 264.7 macrophage cells. Anti-inflammatory and analgesic activities in vivo were assessed with carrageenan-induced paw edema and acetic acid-stimulated writhing in mice models. RESULTS: 23 MIAs including four new compounds were obtained and structurally established. Most of isolates showed significant anti-inflammatory effects in vitro by inhibiting inflammatory mediators (COX-2, IL-1ß, and TNF-α). Further pharmacological evaluation in vivo revealed that 12-hydroxy-19(R)-hydroxy-ibophyllidine (1) and 11,12-methylenedioxykopsinaline N4-oxide (5) remarkably decreased the number of writhing, while kopsinic acid (8), (-)-kopsinilam (12), and normavacurine-21-one (20) significantly relieved paw edema, respectively, even better than the positive control aspirin. CONCLUSIONS: The in vitro and in vivo findings supported the traditional use of K. officinalis with respect to its anti-inflammatory and analgesic effect, as well as provided potent bioactive MIAs for further chemical modification and pharmacological investigation.

A natural acylphloroglucinol triggered antiproliferative possessions in HEL cells by impeding STAT3 signaling and attenuating angiogenesis in transgenic zebrafish model.

Leukemia is responsible for a reason of death, globally. Even though there are several treatment regimens available in the clinics against this disease, a perfect chemotherapeutic agent for the same is still under investigation. Natural plant-derived secondary metabolites are used in clinics to treat leukemia for better benefits with reduced side-effects. Likely, several bioactive compounds from Callistemon sp. were reported for their bioactive benefits. Furthermore, acylphloroglucinol derivatives from Callistemon salignus, showed both antimicrobial and cytotoxic activities in various adherent human cancer cell lines. Thus, in the present study, a natural acylphloroglucinol (2,6-dihydroxy-4-methoxyisobutyrophenone, L72) was tested for its antiproliferative efficacy in HEL cells. The MTT and the cell cycle analysis study revealed that L72 treatment can offer antiproliferative effects, both time and dose-dependent manner, causing G2/M cell cycle arrest. The western blot analysis revealed that L72 treatment triggered intrinsic apoptotic machinery and activated p21. Likewise, L72 could downregulate the gene expressions of XIAP, FLT3, IDH2, and SOD2, which was demonstrated by qPCR analysis, thus promoting its antiproliferative action. The L72 could impede STAT3 expression, which was evidenced by insilico autodock analysis and western blot analysis using STAT3 inhibitor, Pimozide. The treatment of transgenic (Flk-1+/egfr+) zebrafish embryos resulted in the STAT3 gene inhibition, proving its anti-angiogenic effect, as well. Thus, the study revealed that L72 could act as an antiproliferative agent, by triggering caspase-dependent intrinsic apoptosis, reducing cell proliferation by attenuating STAT3, and activating an anti-angiogenic pathway via Flk-1inhibition.

Previously undescribed pyridyl-steroidal glycoalkaloids and 23S,26R-hydroxylated spirostanoid saponin from the fruits of Solanum violaceum ortega and their bioactivities.

Three previously undescribed pyridyl-steroidal glycoalkaloids, solanindiosides A‒C, one rare 23S,26R-hydroxylated spirostanoid saponin, and two steroidal alkaloid aglycones, solanindins A and B, derived from the acid hydrolysis of solanindiosides A‒C, were isolated from the fruits of Solanum violaceum, together with five known analogues, including two rare steroidal glycosides, two lignans and a diterpene. Structurally, they comprise a 16ß-methoxy-23-deoxy-22,26-epimino-cholest-type skeleton moiety, and a 16ß-methoxy-3,23-dideoxy-22,26-epimino-cholest-3,5-dien derivative. The hitherto undescribed structures were established on the basis of extensive spectroscopic analyses. Configurations of sugar moieties were resolved by chemical derivations. Solanindiosides A‒C, (22R,23S,25R,26R)-spirost-5-ene-3ß,23,26-triol3-O-ß-d-xylopyranosyl-(1→3)-ß-d-glucopyranoside, solanindins A and B, and (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol were evaluated for their cytotoxic and antibacterial activities. (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol showed the most potent cytotoxic activity against MCF-7 cells (IC50 = 4.386 ± 0.098 µM), while solanindin B displayed some inhibitory effects against Staphylococcus aureus Rosenbach with MIC50 value of 37.32 ± 0.793 µM. In addition, (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol induced dose dependent apoptosis effect in MCF-7 cells.

Diverse isoquinolines with anti-inflammatory and analgesic bioactivities from Hypecoum erectum.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypecoum erectum has been used extensively in folk medicine to treat inflammation, fever, and pain. However, few investigations have been carried out on the biological activities related to its traditional use. The chemical constituents of this plant along with their anti-inflammatory and analgesic effects have yet to be revealed. AIM OF THE STUDY: This study aimed to support the traditional use of H. erectum by first assessing its anti-inflammatory and analgesic effects and then investigating its chemical constituents to identify any anti-inflammatory and/or analgesic compounds. MATERIAL AND METHODS: The in vivo anti-inflammatory and analgesic activities of the MeOH extract (ME), total alkaloid (AL), and non-alkaloid (Non-AL) fractions of H. erectum at doses of 200, 100, and 50 mg/kg and four major constituents (20, 21, 22, and 27) at doses of 100 and 50 mg/kg delivered via intragastrical administration were evaluated using carrageenan-induced paw edema and acetic acid-stimulated writhing animal models. A phytochemical study of the bioactive (AL) fraction was conducted using various chromatographic techniques, and the structures of the obtained isoquinolines were identified by multiple spectroscopic analyses and quantum chemical computations. Moreover, the anti-inflammatory activities of all the isolates were assessed in vitro based on the suppression of lipopolysaccharide-activated inflammatory mediators (COX-2, IL-1ß, and TNF-α) in RAW 264.7 macrophage cells. RESULTS: At the dose of 200 mg/kg, the three fractions (ME, AL, and Non-AL) of H. erectum ameliorated the paw edema by carrageenan-stimulated and reduced the number of writhing by acetic acid-induced in mice compared to the model group, with the AL fraction showing the most potent effects. Subsequent phytochemical investigation of the AL fraction led to the isolation of six new isoquinoline alkaloids (1-6) as well as 23 known analogues (7-29). However, compared to common isoquinolines, compounds 1-4 possess an additional nitrogen atom, while compound 5 has two additional nitrogen atoms. These additional atoms enrich the diversity of natural isoquinoline alkaloids. Further pharmacological evaluation in vivo revealed that the four major constituents (20, 21, 22, and 27) significantly relieved paw edema at 100 mg/kg, while protopine (20) and oxyhydrastinin (27) remarkably decreased the number of writhing at 100 mg/kg. In addition, most of the isolates displayed anti-inflammatory effects, as indicated by the inhibition of inflammatory mediators (COX-2, IL-1ß, and/or TNF-α) in vitro at a treatment concentration of 5 µg/mL. trans-benzindenoazepines (13), protopine (20), and 1,3,6,6-tetramethyl-5,6,7,8-tetrahyboisoquiolin-8-one (25) showed comparable anti-inflammatory activity to dexamethasone by inhibiting the secretion of IL-1ß. CONCLUSIONS: This investigation validated the traditional use of H. erectum by assessing its anti-inflammatory and analgesic effects. Phytochemical investigation revealed the diversity and novelty of the natural isoquinoline alkaloids in H. erectum. Four major isoquinolines were identified as the bioactive constituents of H. erectum. The findings provide scientific justification to support the traditional application of H. erectum for treating inflammatory and pain disorders.

Paris Saponin VII Induces Apoptosis and Cell Cycle Arrest in Erythroleukemia Cells by a Mitochondrial Membrane Signaling Pathway.

BACKGROUND AND PURPOSE: Leukemia is considered a top-listed ailment, according to WHO, which contributes to the death of a major population of the world every year. Paris Saponin VII (PS), a saponin which was isolated from the roots of Trillium kamtschaticum, from our group, was reported to provide hemostatic, cytotoxic and antimicrobial activities. However, its molecular mechanism underlying the anti-proliferative effects remains unclear. Thus, this study hypothesized to assess that mechanism in PS treated HEL cells. METHODS: The MTT assay was used to analyze the PS inhibited cell viability in the HEL cells. We further found that PS could induce S phase cell cycle arrest through flow cytometry as well as the western blot analysis of intrinsic and extrinsic apoptotic molecules. RESULTS: The MTT assay showed the IC50 concentration of PS as 0.667µM. The study revealed that PS treatment inhibits cell proliferation dose-dependently. It further caused mitochondrial membrane potential changes by PS treatment. Mechanistic protein expression revealed a dose-dependent upsurge for Bid and Bim molecules, while Bcl2 and PARP expression levels were significantly (P<0.05) down-regulated in PS treated HEL cells resulting in caspase -3 release and increased the Bim levels upon 24h of incubation. CONCLUSION: These findings indicate that PS possesses an excellent anti-leukemic activity via the regulation of the mitochondrial pathway, leading to S phase cell cycle arrest and caspase-dependent apoptosis, suggesting it as a potential alternative chemotherapeutic agent for leukemia patients.

Polymethylated Phloroglucinol Meroterpenoids from Rhodomyrtus tomentosa and Their Antibacterial and Acetylcholinesterase Inhibitory Effects.

Rhotomentodiones C-E, three new polymethylated phloroglucinol meroterpenoids with diverse configurations, were isolated from the twigs and leaves of Rhodomyrtus tomentosa. Their structures and absolute configurations were established mainly by means of comprehensive spectroscopic data and electron circular dichroism (ECD) calculation. Among them, Rhotomentodione D (2) exhibited both antibacterial activity with an MIC value of 12.5 µg/mL against Propionibacterium acnes and AChE inhibitory activity with an IC50 value of 22.9 µm.

Anti-inflammatory and analgesic activities of Neolamarckia cadamba and its bioactive monoterpenoid indole alkaloids.

ETHNOPHARMACOLOGICAL RELEVANCE: Neolamarckia cadamba has been used traditionally to treat inflammation, fever, and pruritus in the Dai ethnopharmacy in Yunnan province, P.R. China. However, according to literature survey, the action basis of anti-inflammatory and analgesic activities of this plant were rarely reported, which accounts for the original intentions of this investigation. AIM OF THE STUDY: The study aimed to investigate the anti-inflammatory and analgesic action of methanolic extract (ME), ethyl acetate (EA), and aqueous (AQS) fractions of N. cadamba and further explore the accurate compounds responsible for the activities of EA fraction. MATERIALS AND METHODS: The in vivo anti-inflammatory and analgesic activities of ME, EA, and AQS fractions at the doses of 200 and 400 mg/kg and two major constituents (compounds 5 and 7) at 50 and 100 mg/kg via intragastrically administrated, respectively, were evaluated by carrageenan-induced paw edema and acetic acid-stimulated writhing animal models. Aspirin (ASP) was used as the positive control at the dose of 200 mg/kg. The monoterpenoid indole alkaloids (MIAs) in EA fraction were phytochemically studied utilizing chromatographic techniques, and their structures and absolute configurations were established on the basis of multiple spectroscopic analyses and quantum computational chemistry method. Moreover, the in vitro anti-inflammatory activities of all the isolates were assessed by suppressing releases of LPS-activated inflammatory mediators (TNF-α, IL-1ß, and COX-2) in RAW 264.7 macrophage cells at a concentration of 10 µg/mL. Dexamethasone (DXM) was used as the positive control. RESULTS: Three fractions (ME, EA, and AQS) significantly ameliorated the paw edema caused by carrageenan and reduced the number of writhing induced by acetic acid in comparison to the control group at the doses of 200 and/or 400 mg/kg (in vivo). Subsequent phytochemical investigation of EA fraction led to the structural characterization of four new monoterpenoid indole alkaloids, neocadambines A-D (1-4), as well as eight known analogues (5-12). Neocadambine A possesses a novel 14-nor-MIA skeleton that could be derived from the corynantheine-type MIAs via oxidative cleavage of C3-C14 bond and subsequently degradation of C14. Moreover, the structure of a bioactive known MIA, cadambine acid (6), was reassigned by analysis of its NMR spectroscopic data. Further biological assays revealed that the major constituent 3ß-dihydrocadambine (7) significantly relieved the paw edema and decreased the number of writhing at 100 mg/kg in vivo. In addition, most of the isolates displayed remarkable in vitro anti-inflammatory effects by inhibiting the secretion of aforementioned inflammatory mediators (COX-2, IL-1ß, and TNF-α) at a concentration of 10 µg/mL, and compounds 4, 7, and 9 showed better anti-inflammatory effects than that of positive control, dexamethasone. CONCLUSIONS: This study further validated the anti-inflammatory and analgesic activities of N. cadamba, and revealed that monoterpenoid indole alkaloids could partly contribute to the efficacy of this ethnodrug. The major constituent 3ß-dihydrocadambine (7) showed significant anti-inflammatory activities both in vitro and in vivo, which suggested that it could be a promising anti-inflammatory lead compound. Our findings provided scientific justification to support the traditional application of N. cadamba for treating inflammatory and nociceptive disorders.

Molecular networking uncovers steroidal saponins of Paris tengchongensis.

Based on a method combining the LC-MS/MS molecular networking strategy with the conventional means of phytochemical research, the chemical constituents and the availability of Paris tengchongensis, a new species found in 2017 from Yunnan Province, were investigated for the first time. The molecular networking showed that this species contained the characteristic steroidal glycosides of the genus Paris by comparison of those of Paris polyphylla var. yunnanensis. Furthermore, the detailed investigation on the 80% EtOH extract of its rhizomes resulted to the isolation of twenty steroidal glycosides including three new spirostane-type saponins, named paristengosides A-C (1-3). Their structures were confirmed by spectroscopic analyses (HRMS and NMR) and chemical methods. The new isolates were evaluated for their cytotoxicities against two human cancer cell lines (HEL and MDA-MB-231), anti-inflammatory effects on a lipopolysaccharide (LPS)-stimulated NO production model in RAW264.7 macrophages, anti-AChE, and antimicrobial activities. The results from the molecular networking and the investigation on the chemical constituents suggested that P. tengchongensis can be used as a potential resource of Rhizoma Paridis.

Phenolic Amides with Immunomodulatory Activity from the Nonpolysaccharide Fraction of Lycium barbarum Fruits.

The fruits of Lycium barbarum have a long history as an edible and medicinal food in Asian regions and have multiple consumption methods; the polysaccharides (LBPs) are commonly considered as their major immunological constituents. The current study revealed that the total phenolic amide moieties from L. barbarum fruits showed greater potential immunomodulatory activity in vivo than did LBPs. Through subsequent investigation on the immunological bioactive phenolic amides, three new phenolic amides, lyciumamides L-N (1-3), as well as 12 analogues, were obtained from the total phenolic amide fraction. Extensive spectroscopic methods were used to elucidate the new structures. Compounds 4-6 and 15 significantly promoted LPS-stimulated B splenocyte, while compounds 4-6 displayed accelerative effects on the proliferation of Con A-stimulated T lymphocytes at a concentration of 20.0 µg/mL. These data indicated that extracts from L. barbarum fruits enriched with phenolic amides could be developed as a nutritional dietary supplement for immunocompromised individuals.

Racemic immunosuppressive seco-aporphine derivatives from Thalictrum wangii.

Thallactones A (1) and B (2), enantiomeric aporphine alkaloids with rare cleaved rings A and B, as well as thaliglucine N-oxide (3) and their biosynthetically related precursor, northalphenine (4), were isolated from the whole plant of Thalictrum wangii. Their structures with absolute configurations were elucidated by spectral techniques and electronic circular dichroism (ECD). Moreover, compounds 1, 3, and northalphenine inhibited concanavalin A (Con A)-stimulated proliferation of mice splenocyte significantly in a dose-dependent manner.

Transcriptome analyses of Paris polyphylla var. chinensis, Ypsilandra thibetica, and Polygonatum kingianum characterize their steroidal saponin biosynthesis pathway.

Steroidal saponins, one of the most diverse groups of plant-derived natural products, elicit biological and pharmacological activities; however, the genes involved in their biosynthesis and the corresponding biosynthetic pathway in monocotyledon plants remain unclear. This study aimed to identify genes involved in the biosynthesis of steroidal saponins by performing a comparative analysis among transcriptomes of Paris polyphylla var. chinensis (PPC), Ypsilandra thibetica (YT), and Polygonatum kingianum (PK). De novo transcriptome assemblies generated 57,537, 140,420, and 151,773 unigenes from PPC, YT, and PK, respectively, of which 56.54, 47.81, and 44.30% were successfully annotated, respectively. Among the transcriptomes for PPC, YT, and PK, we identified 194, 169, and 131; 17, 14, and 26; and, 80, 122, and 113 unigenes corresponding to terpenoid backbone biosynthesis; sesquiterpenoid and triterpenoid biosynthesis; and, steroid biosynthesis pathways, respectively. These genes are putatively involved in the biosynthesis of cholesterol that is the primary precursor of steroidal saponins. Phylogenetic analyses indicated that lanosterol synthase may be exclusive to dicotyledon plant species, and the cytochrome P450 unigenes were closely related to clusters CYP90B1 and CYP734A1, which are UDP-glycosyltransferases unigenes homologous with the UGT73 family. Thus, unigenes of ß-glucosidase may be candidate genes for catalysis of later period modifications of the steroidal saponin skeleton. Our data provide evidence to support the hypothesis that monocotyledons biosynthesize steroidal saponins from cholesterol via the cycloartenol pathway.

Isolation and Synthesis of Novel Meroterpenoids from Rhodomyrtus tomentosa: Investigation of a Reactive Enetrione Intermediate.

Rhodomyrtusials A-C, the first examples of triketone-sesquiterpene meroterpenoids featuring a unique 6/5/5/9/4 fused pentacyclic ring system were isolated from Rhodomyrtus tomentosa, along with several biogenetically-related dihydropyran isomers. Two bis-furans and one dihydropyran isomer showed acetylcholinesterase (AChE) inhibitory activity. Structures of the isolates were unambiguously established by a combination of spectroscopic data, ECD analysis, and total synthesis. Bioinspired total syntheses of six isolates were achieved in six steps utilizing a reactive enetrione intermediate generated in situ from a readily available hydroxy-endoperoxide precursor.

Untiring Researches for Alternative Resources of Rhizoma Paridis.

Rhizoma Paridis (RP, ), a traditional Chinese medicine, is the rhizoma of Paris polyphylla var. yunnanensis (PPY) or P. polyphylla var. chinensis which are widely used as important raw materials for several Chinese patent drugs. However, the wild resources of these herbs have become less and less due to their slow-growing characteristics and previously excessive excavation. This review covers untiring investigations on alternative resources of RP by our research group over the past decades, including non-medicinal parts of PPY as well as other plants of Liliaceae and Liliflorae families. The arial parts of PPY and the whole plants of Trillium kamtschaticum might be alternative resources for RP based on the fact that they shared the same or similar saponins and bioactivities.

Seeing the light: Shifting from wild rhizomes to extraction of active ingredients from above-ground parts of Paris polyphylla var. yunnanensis.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried rhizomes of Paris polyphylla var. yunnanensis are widely used in traditional Chinese medicine (TCM) as hemostatic, antitumor, and antimicrobial agents. More than 70 Chinese patent medicines are based on P. polyphylla var. yunnanensis rhizomes. Steroidal saponins are considered as the main active ingredients of these rhizomes. However, wild populations of P. polyphylla var. yunnanensis are greatly threatened due to the illegal wild harvest and over-utilization of the rhizomes. In contrast, the renewable above-ground parts (leaves and stems) of P. polyphylla var. yunnanensis are usually thrown away as waste material, whether from wild or cultivated material. AIM OF THE STUDY: The aim of this study was to use HPLC analyses of chemical constituents and bioactive assays to assess whether the above-ground parts could be an alternative source of active ingredients to the rhizomes of P. polyphylla var. yunnanensis. MATERIALS AND METHODS: The saponin components of the rhizomes and above-ground parts of P. polyphylla var. yunnanensis were analyzed by HPLC-UV. The total saponins extracted from the rhizomes and above-ground parts of P. polyphylla var. yunnanensis were evaluated for their hemostatic, cytotoxic, and antimicrobial activities by using the rabbit blood in vitro based on turbidimetric method, MTT assay method, and a dilution antimicrobial susceptibility test method, respectively. RESULTS: Four bioactive spirostanol saponins (paris saponins I, II, VI, and VII) were detected in the total saponins from the rhizomes and above-ground parts of P. polyphylla var. yunnanensis, which indicated they should have similar pharmacological properties. The bioactive assays revealed that both the parts of P. polyphylla var. yunnanensis exhibited the same hemostatic, cytotoxic, and antimicrobial effects. CONCLUSION: Our results revealed that based on saponin content in the above-ground parts of P. polyphylla var. yunnanensis and the requirements stipulated in 2015 of Chinese Pharmacopoeia, the above-ground parts (especially its leaves) can be an alternative and more sustainable source of active ingredients compared to the rhizomes.

Rare Hybrid Dimers with Anti-Acetylcholinesterase Activities from a Safflower (Carthamus tinctorius L.) Seed Oil Cake.

Safflower (Carthamus tinctorius) is commercially cultivated for vegetable oil extracted from the seeds. However, during the production process of seed oil, a large amount of the oil cake is thrown away or fermented as fertilizer to improve the homing rate of pigeons. Therefore, to solve the ecological problem and develop its new function, we investigated the chemical constituents of a safflower seed oil cake, and six new hybrid dimers, (±)-carthatins A-F (1-6, respectively), with a phenylpropanoid and a feruloylserotonin fused via a dihydrofuran ring, together with four known compounds, including sinapyl alcohol (7), coniferyl alcohol (8), serotobenine (9), and feruloylserotonin (10), were isolated. The extensive nuclear magnetic resonance spectra, combined with electronic circular dichroism analysis and chiral high-performance liquid chromatography, allowed the complete structural assignments of (±)-carthatins A-F. Moreover, we evaluated their anti-acetylcholinesterase activities. Racemic carthatins A and B (1 and 2, respectively) showed anti-acetylcholinesterase effects with IC50 values of 17.96 and 66.83 µM, respectively. To some extent, our findings provide a new scaffold of acetylcholinesterase inhibitors, which could be beneficial for developing therapeutic molecules for the treatment of Alzheimer's disease and supporting folk application of a safflower seed oil cake.