Cucurbitane-type Triterpenoids Research Articles

Therapeutic Potential of Momordicine I from Momordica charantia: Cardiovascular Benefits and Mechanisms.

Momordica charantia (bitter melon), a traditional medicinal plant, has been demonstrated to have potential in managing diabetes, gastrointestinal problems, and infections. Among its bioactive compounds, momordicine I, a cucurbitane-type triterpenoid, has attracted attention due to its substantial biological activities. Preclinical studies have indicated that momordicine I possesses antihypertensive, anti-inflammatory, antihypertrophic, antifibrotic, and antioxidative properties, indicating its potential as a therapeutic agent for cardiovascular diseases. Its mechanisms of action include modulating insulin signaling, inhibiting inflammatory pathways, and inducing apoptosis in cancer cells. The proposed mechanistic pathways through which momordicine I exerts its cardiovascular benefits are via the modulation of nitric oxide, angiotensin-converting enzymes, phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt), oxidative stress, apoptosis and inflammatory pathways. Furthermore, the anti-inflammatory effects of momordicine I are pivotal. Momordicine I might reduce inflammation through the following mechanisms: inhibiting pro-inflammatory cytokines, reducing adhesion molecules expression, suppressing NF-κB activation, modulating the Nrf2 pathway and suppressing c-Met/STAT3 pathway. However, its therapeutic use requires the careful consideration of potential side effects, contraindications, and drug interactions. Future research should focus on elucidating the precise mechanisms of momordicine I, validating its efficacy and safety through clinical trials, and exploring its pharmacokinetics. If proven effective, momordicine I could considerably affect clinical cardiology by acting as a novel adjunct or alternative therapy for cardiovascular diseases. To date, no review article has been published on the role of bitter-melon bioactive metabolites in cardiovascular prevention and therapy. The present work constitutes a comprehensive, up-to-date review of the literature, which highlights the promising therapeutic potential of momordicine I on the cardiovascular system and discusses future research recommendations.

Major Bitter-Tasting Compounds from the Dichloromethane Fraction of Bitter Gourd (Fruit of Momordica charantia L.) Extract and Their Precursors.

The unripe fruit of the plant Momordica charantia L., commonly known as bitter gourd or bitter melon, is a popular vegetable and medical herb in many parts of the world and is characterized by its strong bitter taste. In our endeavor to decode its bitter taste, the dichloromethane fraction of 75% methanol extract of bitter gourd was found to be intensely bitter. Combining sensory analysis-guided fractionation and newly developed comparative high-pressure liquid chromatography (HPLC) analysis-guided purification led to the isolation of five known compounds including momordicoside L (1), (23E)-3β-O-malonyl-7β,25-dihydroxycucurbita-5,23-dien-19-al (2), 3-O-β-d-allopyranosyl-7β,25-dihydroxycucurbita-5,23(E)-dien-19-al (3), momordicine IV (5), and charantoside B (6) and three new compounds 3-O-β-d-3-ketoglucopyranosly-7β,25-dihydroxycucurbita-5,23(E)-dien-19-al (4), 6'-O-malonylmomordicoside L (7), and 6'-O-malonylmomordicine IV (8) from bitter gourd. Sensory analysis revealed compounds 3-8 had strong bitter taste with their bitter taste recognition thresholds in the range between 3.6 (4) and 13.6 ppm (6) in 3% ethanol. UPLC-MS/MS quantification showed that their concentration in bitter gourd ranged from 16.5 ± 1.3 mg/kg (4) to 214.8 ± 14.0 mg/kg (6) on a dry weight basis. Calculation of the dose-over-threshold (DoT) factor showed that momordicine IV (5) and charantoside B (6) should be considered as bitter principles of bitter gourd. In addition, the study also demonstrated the ubiquity of the isomerization reaction in the side chain of cucurbitane-type triterpenoids. Many isolated compounds were the isomerized products of their natural precursors, and these precursors should be the primary bitterness contributors of fresh fruits. In addition, comparative HPLC analysis-guided purification could be a practical approach for the fast isolation of acid-labile precursors.

Two new cucurbitane-type triterpenoid saponins from the fruit of Citrullus colocynthis

Two new cucurbitane-type triterpenoid saponins, 2,20β,22β-trihydroxy-16α,23(R)-epoxycucurbita-1,5,24-triene-3,11-dione 2-O-β-D-glucopyranoside (1), 2,20β,22α-trihydroxy-16α,23(S)-epoxycucurbita-1,5,11,24-tetraene-3-one 2-O-β-D-glucopyranoside (2) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10 μM against paracetamol-induced HepG2 cell damage.

Target and non-target analysis with molecular network strategies for identifying potential index compounds from Momordica charantia L. for alleviating non-alcoholic fatty liver

The cucurbitane-type triterpenoids of Momordica charantia Linn. have blood lipid lowering effect and thereby improving non-alcoholic fatty liver. In this study, microwave-assisted extraction efficiently obtained these compounds which were further confirmed by the use of UPLC-MS/MS for target analysis and LC-HRMS for non-target analysis, combining GNPS techniques. The results indicated that the content of cucurbitane-type triterpenoids in bitter melon Hualien No. 5 was the highest among the others. Except for the immature whole fruit, the other plant parts such as fruits, seeds, vines and the whole plant of Hualien No. 5 with different maturity levels of immature, mature and overripe can significantly inhibit lipid accumulation in hepatocytes induced by oleic acid. The vines were proven as the most significant among the others where the active components for improving non-alcoholic fatty liver were rapidly screened and identified as 3β,7β,25-trihydroxycucurbita-5,23 (E)-dien-19-al and Momordicine II through non-target analysis, multivariate analysis and molecular network.

Isolation of two new cucurbitane-type triterpenoids from Kedrostis gijef

Two new cucurbitane-type triterpenoids (2,3), together with two known compounds (1,4), were isolated from the aerial parts of Kedrostis gijef. The structure of all compounds was elucidated based on NMR, HRESIMS analyses, and by comparison with the literature. Additionally, the cytotoxic activity against HeLa, Caco-2, and SH-SY5Y cell lines was determined using MTT colorimetric assay.

Structurally diverse cucurbitane-type triterpenoids from the tubers of Hemsleya chinensis with cytotoxic activity

Ten previously undescribed cucurbitane-type triterpenoids, namely hemslyencins A−F (1–6) and hemslyencosides A−D (7−10), together with twenty previously reported compounds (11–30), were isolated from the tubers of Hemsleya chinensis. Their structures were elucidated by unambiguous spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR data). Hemslyencins A and B (1 and 2) possessing unique 9, 11-seco-ring system with a six-membered lactone moiety, were the first examples among of the cucurbitane-type triterpenoids, and hemslyencins C and D (3 and 4) and hemslyencoside D (10) are the infrequent pentacyclic cucurbitane triterpenes featuring a 6/6/6/5/6 fused system. The cytotoxic activities of all isolated compounds were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cells, and their structure-activity relationships (SARs) was discussed as well. Compounds 17, 25, and 26 showed significant cytotoxic effects with IC50 values ranging from 1.31 to 9.89 μM, among which compound 25 induced both apoptosis and cell cycle arrest at G2/M phase in a dose dependent manner against MCF-7 cells.

Sesquiterpenoids and hexanorcucurbitacin from Aquilaria malaccensis agarwood with anti-inflammatory effects by inhibiting the STAT1/AKT/MAPK/NLRP3 pathway.

Seven unknown compounds 1-7, including four sesquiterpenoids, one azulene-type, one indene-type, and one rare hexanorcucurbitacin, together with eleven knowns ones (8-16), were isolated from the agarwood chips of Aquilaria malaccensis. The structures of the isolated compounds were elucidated by extensive spectroscopic methods such as mass spectrometry, UV, IR, NMR spectroscopy. The precise stereo-chemical configurations of new compounds were determined by calculated ECD spectra data, as well as a single-crystal X-ray diffraction analysis. The isolated compounds 1-7 were evaluated by estimating the levels of nitric oxide (NO), TNF-α, and the expression of enzyme iNOS, and COX-2. Among them, a rare hexanortriterpenoid (7) derived from a cucurbitane-type triterpenoid showed the significantly attenuated neuro-inflammatory effects via the STAT1/AKT/MAPK/NLRP3 signaling pathway on the mechanistic studies.

Metabolism of Two Mogroside Isomers, Mogroside III and Mogroside IIIE, in Normal and Drug-Metabolizing Enzyme-Induced Rats.

Mogrosides III (1) and IIIE (2) are two important bioactive cucurbitane-type triterpenoid triglycosides in the edible fruits of Siraitia grosvenorii (Swingle), which are isomers and have only a minor difference in their structures. To clarify the effects of structural difference and drug-metabolizing-enzyme induction on their metabolism in vivo, their metabolites in normal rats and drug-metabolizing-enzyme-induced rats were tentatively identified and semiquantified by using the HPLC-DAD-ESI-IT-TOF-MSn technique. Totally, 76, 78, 96, and 121 metabolites of mogrosides were identified in the NIII (normal rats orally administered with mogroside III), NIIIE (normal rats orally administered with mogroside IIIE), EIII (drug-metabolizing-enzyme-induced rats orally administered with mogroside III), and EIIIE (drug-metabolizing-enzyme-induced rats orally administered with mogroside IIIE) groups, respectively. The metabolite differences among these groups indicated that their minor structural differences are responsible for the significant differences in their metabolites, and the induction of drug-metabolizing enzymes significantly increased the number of their metabolites. These findings would improve our understanding of the in vivo processes of mogrosides III and IIIE as well as their interactions with other food bioactive components or drugs.

Investigating the multitargeted anti-diabetic potential of cucurbitane-type triterpenoid from Momordica charantia: an LC-MS, docking-based MM\\GBSA and MD simulation study

Type 2 diabetes accounts for the largest percentage of all diabetic cases worldwide. Cucurbitane-type triterpenes are mainly found in Momordica charantia and possess excellent pharmacological activities. This study was designed to identify cucurbitane-type triterpene from Momordica charantia using Liquid Chromatography-Mass Spectrometry (LC-MS) analysis, examine its anti-diabetic property with molecular docking against diabetes enzymes (alpha-amylase, alpha-glucosidase, dipeptidyl dipeptidase IV and peroxisome proliferator-activated receptor gamma). The stability and interactions of the docked complexes were investigated using molecular dynamics simulation, while the pharmacokinetic and toxicity profile of the ligand was examined using an ADMET server. (23E)-Cucurbita-5,23,25-triene-3,7-dione (CUB) was identified from the LC-MS profiling of the methanolic extract of M. charantia. The molecular docking studies showed that the identified phytochemical elicited good binding energy against all the target receptors. The RMSD and RMSF plots obtained from the 100 ns molecular dynamics simulation showed that the ligand was stable and established substantial interactions with the amino acid residues of the diabetes enzymes which were confirmed by the MM\\GBSA computations. The pharmacokinetic and toxicity properties of the ligand showed it was safer as an anti-diabetic drug candidate. Extensive isolation, in vitro and in vivo studies of the ligand against the diabetic enzymes is recommended.Communicated by Ramaswamy H. Sarma

Three new cucurbitane-type triterpenoid glycosides from Citrullus colocynthis and their anti-inflammatory activity

Three new cucurbitane-type triterpenoid glycosides were separated from the ethyl acetate extract of Citrullus colocynthis by a variety of chromatographic techniques. According to the data of NMR, HR-ESI-MS, and/or comparison with the reported data, the three novel cucurbitane-type triterpenoid glycosides were identified as colocynthenin E(1), colocynthenin G(2), and colocynthenin H(3). The cell inflammation model was established with RAW264.7 macrophages exposed to lipopolysaccharide and then used to determine the anti-inflammatory activities of the three compounds. Compounds 2 and 3 showed mild anti-inflammatory activities with the IC_(50) of 48.21 and 40.11 μmol·L~(-1), respectively, compared with that(IC_(50)=7.57 μmol·L~(-1)) of the positive control dexamethasone.

Trichosanates A–G and cucurbitacins W–Y, anticomplement monoterpenoids and cucurbitane-type triterpenoids from the pericarps of Trichosanthes kirilowii

The pericarps of Trichosanthes kirilowii are often used to treat cough in traditional Chinese medicine, and its ethanol extract exhibited effective therapeutic effects on acute lung injury (ALI) in vivo caused by H1N1. An anticomplement activity-guided fractionation on the extract resulted in the isolation of ten new terpenoids, including seven monoterpenoids, trichosanates A–G (1–7), and three cucurbitane-type triterpenoids, cucurbitacins W–Y (8–10), as well as eleven known terpenoids (11–21). The new terpenoids’ structures were determined by spectroscopic analysis, X-ray crystallographic analysis (1), electronic circular dichroism (ECD) analysis and calculations (2–10). Twelve monoterpenoids (1–7 and 11–15) and five cucurbitane-type triterpenoids (8–10, 18, and 20) exhibited anticomplement activity in vitro. For the monoterpenoids, the long aliphatic chain substituents might enhance their anticomplement activity. Additionally, two representative anticomplement terpenoids, 8 and 11, obviously attenuated H1N1-induced ALI in vivo by inhibiting complement overactivation and reducing inflammatory responses.

Identification and Isolation of α-Glucosidase Inhibitors from Siraitia grosvenorii Roots Using Bio-Affinity Ultrafiltration and Comprehensive Chromatography.

The discovery of bioactive compounds from medicinal plants has played a crucial role in drug discovery. In this study, a simple and efficient method utilizing affinity-based ultrafiltration (UF) coupled with high-performance liquid chromatography (HPLC) was developed for the rapid screening and targeted separation of α-glucosidase inhibitors from Siraitia grosvenorii roots. First, an active fraction of S. grosvenorii roots (SGR2) was prepared, and 17 potential α-glucosidase inhibitors were identified based on UF-HPLC analysis. Second, guided by UF-HPLC, a combination of MCI gel CHP-20P column chromatography, high-speed counter-current countercurrent chromatography, and preparative HPLC were conducted to isolate the compounds producing active peaks. Sixteen compounds were successfully isolated from SGR2, including two lignans and fourteen cucurbitane-type triterpenoids. The structures of the novel compounds (4, 6, 7, 8, 9, and 11) were elucidated using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectrometry. Finally, the α-glucosidase inhibitory activities of the isolated compounds were verified via enzyme inhibition assays and molecular docking analysis, all of which were found to exhibit certain inhibitory activity. Compound 14 exhibited the strongest inhibitory activity, with an IC50 value of 430.13 ± 13.33 μM, which was superior to that of acarbose (1332.50 ± 58.53 μM). The relationships between the structures of the compounds and their inhibitory activities were also investigated. Molecular docking showed that the highly active inhibitors interacted with α-glucosidase through hydrogen bonds and hydrophobic interactions. Our results demonstrate the beneficial effects of S. grosvenorii roots and their constituents on α-glucosidase inhibition.

Heterodimers with a cucurbitane-type triterpenoid skeleton from the branches of Elaeocarpus dubius

Four undescribed and two known cucurbitane-type triterpenoids, including two heterodimers, elaeocarpudubins A and B, were isolated from the branches of Elaeocarpus dubius (Elaeocarpaceae). The chemical structures of these undescribed isolates were determined by analyses of 1D and 2D NMR and MS data, electronic circular dichroism (ECD) calculations, and chemical transformation. Biogenetically, elaeocarpudubins A and B might be derived from cucurbitacin F through Michael addition with vitamin C and (−)-catechin, respectively. These six isolates were evaluated for their cytotoxic activities against human leukemia HL-60, human lung adenocarcinoma A549, human hepatoma SMMC-7721, human breast cancer MCF-7, human colon cancer SW480, and paclitaxel-resistant A549 (A549/Taxol) cell lines, for their antioxidant properties using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, and for their differentiation effects on nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells. Cucurbitacins F (IC50 of 4.98–38.11 μM) and D (IC50 of 0.03–4.40 μM) showed growth-inhibitory activities against these six cancer cell lines. Elaeocarpudubin B (IC50 of 61.04 μM) and elaeocarpudoside B (IC50 of 6.93 μM) showed antioxidant activities. Elaeocarpudubin B and elaeocarpudoside B also showed neurite outgrowth-promoting activities in PC12 cells at a concentration of 10 μM.

Kaguacidine A: a novel spirohydantoin-containing cucurbitane glycoside from vines of Momordica charantia L.

The spirohydantoin-containing cucurbitane-type triterpenoid, kaguacidine A (1), was isolated and purified from 95% ethanol extract of vines of Momordica charantia L. (Cucurbitaceae). Its unprecedented chemical structure, a spirohydantoin substituent at C-23 of cucurbitane, was elucidated by extensive spectroscopic analyses, including HRESIMS, IR, optical rotation, 1 D- and 2 D-NMR spectra. The possible biosynthetic pathway is deduced and may be attributed to the metabolic activity of microbial symbionts in M. charantia L. Compound 1 was evaluated for anti-inflammatory activity against LPS-induced NO production in RAW 264.7 cells and anti-proliferative activity against four cancer cell lines, including HEp-2, MCF-7, Hep-G2, and WiDr. Compound 1 showed moderate anti-inflammatory activity with an IC50 value of 18.5 ± 0.4 μg/mL and weak anti-proliferative activity against MCF-7, HEp-2, Hep-G2, and WiDr with IC50 values of >40, 33.8 ± 0.6, 31.0 ± 0.7, and 27.0 ± 0.7 μM, respectively.

Diversity of nutrient and nutraceutical contents in the fruits and its relationship to morphological traits in bitter gourd (Momordica charantia L.)

Bitter gourd (Momordica charantia L.), a tropical vegetable crop, has long been used as a food and medicine. Its unripe fruits have anti-diabetic properties due to charantin, a typical cucurbitane-type triterpenoid. The present study aimed to determine diversity in different nutrient (β-carotene and ascorbic acid) and nutraceutical (chlorophyll, total phenols, phenolic acids, flavonoids, radical scavenging activities and charantin) content of matured but unripe fruits of five diverse genotypes and their association with different morphological characters (leaf colour, tendril character, sex form, fruit colour, fruit shape, tubercle character, fruit length, fruit girth and fruit weight) through heat mapping and regression modelling in order to determine the key characters influencing them. The genotypes differed significantly for most of the morphological traits, nutritional and nutraceutical contents and the predominant types of Indian origin (dark green, spindle shaped fruits with sharp tubercles) were associated with high nutrient and most of the nutraceutical contents but comparatively low in charantin content. The predominant types in the region of China, Japan, Indonesia, Korea (whitish yellow, yellowish white, obtuse or roundish-oblong fruit with light ridges or roundish blunt tubercles) were associated with comparatively low nutrient and most of the nutraceutical contents but high in charantin content. Association study identified the morphological characters influencing the phytochemical contents and regression modelling predicted relative significance of those morphological characters on the different nutrient and nutraceutical contents. The study confirmed the effectiveness of combining morphological characters with nutrient and nutraceutical contents that can be utilized to develop functionally rich bitter gourd genotypes.

Cucurbitane-type triterpenoids from the branches and leaves of Elaeocarpus sylvestris

The chemical structures of nine cucurbitane-type triterpenoids from the branches and leaves of Elaeocarpus sylvestris (Elaeocarpaceae), including undescribed 29-hydroxymogroside I E 2 , epimogroside I E 2 , epimogroside I E 1 , 24-oxomogroside I E 1 , and 11- O -acetylmogroside I E 1 , were determined using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. The absolute configuration of 29-hydroxymogroside I E 2 was confirmed by performing an X-ray diffraction analysis. Cucurbitacin D and 11- O -acetylmogroside I E 1 showed cytotoxicity toward human leukemia HL-60, human lung adenocarcinoma A549, human hepatoma SMMC-7721, human breast cancer MCF-7, and human colon cancer SW480 cell lines. The presence of a 11- O -acetyl group might increase the cytotoxicity of this type of triterpenoids. • Five undescribed cucurbitane-type triterpenoids were isolated from Elaeocarpus sylvestris. • Cucurbitacin D and 11-O-acetylmogroside I E 1 showed cytotoxicity toward five cancer cell lines. • The presence of a 11-O-acetyl group might increase the cytotoxicity of this type of triterpenoids.

Triterpenes from Momordica balsamina (African pumpkin): ABCB1 inhibition and synergistic interaction with doxorubicin in resistant cancer cells

Aiming at overcoming multidrug resistance (MDR) in cancer, we have been studying Momordica balsamina, a vegetable known as African pumpkin. Five undescribed cucurbitane-type triterpenoids (balsaminaepoxide, balsaminatriol, balsaminoic acid, balsaminal, and balsaminol G) along with five known cucurbitacins were isolated from the methanol extract of Momordica balsamina aerial parts, whose structures were elucidated by spectroscopic data, mainly 1D and 2D NMR experiments. Compounds were evaluated for their ability as P-glycoprotein (P-gp/ABCB1) inhibitors in multidrug resistant human ABCB1-transfected mouse lymphoma cells (L5178Y, MDR) and resistant human colon adenocarcinoma cells (COLO 320), using the rhodamine-123 exclusion test, by flow cytometry. Several compounds, which were found to be non-cytotoxic, strongly inhibited P-gp efflux activity in a dose-dependent manner in both cell models. In MRD mouse lymphoma cells, balsaminol G and karavilagenin B were the most active, while in resistant colon adenocarcinoma cells, the strongest inhibitory activity was found for balsaminaepoxide, balsaminatriol and karavilagenin C, being several-fold more active than the positive control verapamil. In chemosensitivity assays, in a model of combination chemotherapy, selected compounds showed to interact synergistically with doxorubicin, thus substantiating their potential as MDR reversers. The strongest synergistic interaction was found for balsaminal and balsaminol G.

Cucurbitane triterpenoid entities derived from Hemsleya penxianensis triggered glioma cell apoptosis via ER stress and MAPK signalling cross-talk

In the present study, six new cucurbitane type compounds, including three triterpenoids hemsleyacins P-R (6–7, 13) and three cucurbitane-type triterpenoid glycosides hemsleyaosides L-N (15–17), along with seventeen known cucurbitacin analogues were separated from the root tuber of Hemsleya penxianensis and elucidated based on NMR and HRESIMS. Then, 23 analogues of three types, namely, polyhydroxy-type (I) (1–7), monohydroxy-type (II) (8–13), and glycosides-type (III) (14–23), were assessed for their antitumor activity and structure–activity relationship analysis (SAR). We determined temozolomide (TMZ)-resistant GBM cell was the most sensitive to the tested compounds, and found hemsleyaoside N (HDN) displayed the best antineoplastic potency. Furthermore, we confirmed the anti-glioma activity of HDN in patient-derived recurrent GBM strains, GBM organoid (GBO) and orthotopic nude mouse models. Investigations exploring the mechanism made clear that HDN induced synchronous activation of UPR and MAPK signaling, which triggered deadly ER stress and apoptosis. Taken together, the potent antitumor activity of HDN warrants further comprehensive evaluation as a novel anti-glioma agent.

Momordica charantia L.—Diabetes-Related Bioactivities, Quality Control, and Safety Considerations

Momordica charantia L. (Cucurbitaceae), commonly known as bitter gourd or bitter melon, is widely cultivated in many tropical and subtropical regions of the world, where its unripe fruits are eaten as a vegetable. Apart from its culinary use, M. charantia has a long history in traditional medicine, serving as stomachic, laxative or anthelmintic, and, most notably, for the treatment of diabetes and its complications. Its antidiabetic properties and its beneficial effects on blood glucose and lipid concentrations have been reported in numerous in vitro and in vivo studies, but the compounds responsible for the observed effects have not yet been adequately described. Early reports were made for charantin, a mixture of two sterol glucosides, and the polypeptide p-insulin, but their low concentrations in the fruits or their limited bioavailability cannot explain the observed therapeutic effects. Still, for many decades the search for more reasonable active principles was omitted. However, in the last years, research more and more focused on the particular cucurbitane-type triterpenoids abundant in the fruits and other parts of the plant. This mini review deals with compounds isolated from the bitter gourd and discusses their bioactivities in conjunction with eventual antidiabetic or adverse effects. Furthermore, methods for the quality control of bitter gourd fruits and preparations will be evaluated for their meaningfulness and their potential use in the standardization of commercial preparations.

Novel Triterpenoid Alkaloids With Their Potential Cytotoxic Activity From the Roots of Siraitia grosvenorii

Four novel triterpenoid alkaloids, siragrosvenins A–D (1–4), and two new cucurbitane-type triterpenoids, siragrosvenins E–F (5, 6), together with eight known analogs (7−14), were isolated from the roots of Siraitia grosvenorii. Compounds 1−4 possessed a rare cucurbitane-type triterpenoid scaffold, featuring an extra pyrazine unit via the Strecker reaction in the cucurbitane framework. Compound 5 displayed a 6/6/6/5/6/5-fused polycyclic ring system, with an uncommon fused furan and pyran ring in the side chain. All the structures were characterized by extensive spectroscopic analysis, including HRESIMS, NMR, and X-ray crystallographic data. It is worth noting that the DP4+ analysis method was applied for the first time to determine the absolute configurations of the trihydroxybutyl moiety in the side chain of compounds 1–4. In vitro cytotoxicity screening found that compounds 4, 8, 9, 13, and 14 exhibited remarkable cytotoxic activities against three cell lines with IC50 values ranging from 1.44 to 9.99 μM. Siragrosvenin D shows remarkable cytotoxic activity on MCF-7 cells. As a result, it inhibited the proliferation of MCF-7 cells and reduced their viability via the induction of G2/M phase arrest and significantly induced apoptosis in MCF-7 cells.