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Background: Podocyte injury is a common pathologic mechanism in diabetic kidney disease (DKD) and obesity-related glomerulopathy (ORG). Our previous study confirmed that Inonotus obliquus (IO) improved podocyte injury on DKD rats. The current study explored the pharmacological effects, related mechanisms and possible active components of IO on ORG mice. Methods: Firstly, by combining ultra-high performance liquid chromatography tandem mass spectrometry analysis (UPLC-Q-TOF-MS) with network pharmacology to construct the human protein-protein interaction mechanism and enrich the pathway, which led to discover the crucial mechanism of IO against ORG. Then, ORG mice were established by high-fat diet and biochemical assays, histopathology, and Western blot were used to explore the effects of IO on obesity and podocyte injury. Finally, network pharmacology-based findings were confirmed by immunohistochemistry. The compositions of IO absorbed in mice plasma were analyzed by UPLC-Q-TOF-MS and molecular docking was used to predict the possible active compounds. Results: The network pharmacology result suggested that IO alleviated the inflammatory response of ORG by modulating TNF signal. The 20-week in vivo experiment confirmed that IO improved glomerular hypertrophy, podocyte injury under electron microscopy, renal nephrin, synaptopodin, TNF-α and IL-6 expressions with Western blotting and immunohistochemical staining. Other indicators of ORG such as body weight, kidney weight, serum total cholesterol, liver triglyceride also improved by IO intervention. The components analysis showed that triterpenoids, including inoterpene F and trametenolic acid, might be the pharmacodynamic basis. Conclusion: The research based on UPLC-Q-TOF-MS analysis, network pharmacology and in vivo experiment suggested that the amelioration of IO on podocyte injury in ORG mice via its modulation on TNF signal. Triterpenoids were predicated as acting components. [ABSTRACT FROM AUTHOR]

Yeast has been an indispensable host for synthesizing complex plant-derived natural compounds, yet the yields remained largely constrained. This limitation mainly arises from overlooking the importance of cell and pathway suitability during the optimization of enzymes and pathways. Herein, beyond conventional enzyme engineering, we dissected metabolic suitability with a framework for simultaneously augmenting cofactors and carbon flux to enhance the biosynthesis of heterogenous triterpenoids. We further developed phospholipid microenvironment engineering strategies, dramatically improving yeast's suitability for the high performance of endoplasmic reticulum (ER)-localized, rate-limiting plant P450s. Combining metabolic and microenvironment suitability by manipulating only three genes, NHMGR (NADH-dependent HMG-CoA reductase), SIP4 (a DNA-binding transcription factor)and GPP1 (Glycerol-1-phosphate phosphohydrolase 1), we enabled the high-level production of 4.92 g/L rare licorice triterpenoids derived from consecutive oxidation of β -amyrin by two P450 enzymes after fermentation optimization. This production holds substantial commercial value, highlighting the critical role of establishing cell suitability in enhancing triterpenoid biosynthesis and offering a versatile framework applicable to various plant natural product biosynthetic pathways. By manipulating only three genes, NHMGR , SIP4 and GPP1 , the metabolic and microenvironment suitability between licorice triterpenoid biosynthesis pathway and yeast host were established, enabling the efficient production of licorice triterpenoids in yeast. [Display omitted] [ABSTRACT FROM AUTHOR]

Ursolic acid (UA) and its derivatives have garnered significant attention due to their extensive pharmacological activity. UA is a pentacyclic triterpenoid found in a variety of plants, such as apples, rosemary, thyme, etc., and it possesses a range of pharmacological properties. Researchers have synthesized various derivatives of UA through structural modifications to enhance its potential pharmacological properties. Various in vitro and in vivo studies have indicated that UA and its derivatives possess diverse biological activities, such as anticancer, antifungal, antidiabetic, antioxidant, antibacterial, anti-inflammatory and antiviral properties. This review article provides a review of the biological activities of UA and its derivatives to show their valuable therapeutic properties useful in the treatment of different diseases, mainly focusing on the relevant structure-activity relationships (SARs), the underlying molecular targets/pathways, and modes of action. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the effect of triterpenoids on the development of diabetic nephropathy in an experimental model of diabetes mellitus. For this purpose, a destoned and dehydrated olive oil (DDOO) was used, comparing its effects to a destoned olive oil (DOO). DDOO had a higher triterpenoid content than DOO but an equal content of alcoholic polyphenols. Four study groups (n = 10 animals/group) were formed: healthy rats, diabetic control rats (DRs), and DRs treated orally with 0.5 mL/kg/day of DOO or DDOO for two months. DRs showed impaired renal function (proteinuria, increased serum creatinine, decreased renal creatinine clearance) and morphology (glomerular volume and glomerulosclerosis). These alterations correlated with increased systemic and renal tissue oxidative stress and decreased prostacyclin production. DDOO administration significantly reduced all variables of renal damage, as well as systemic and renal oxidative stress, to a greater extent than the effect produced by DOO. In conclusion, triterpenoid-rich olive oil may prevent kidney damage in experimental diabetes mellitus. [ABSTRACT FROM AUTHOR]

Growth years are important factors that affect the accumulation of secondary metabolites in Eurycoma longifolia roots. This study aimed to investigate the effect of different growth years on the metabolites and gene expression of E. longifolia roots and hairy root cultures. To achieve this, metabolite profiles and candidate transcripts of terpenoid backbone biosynthesis and sesquiterpenoid and triterpenoid pathways of 1- and 11-year old E. longifolia roots and hairy root cultures were obtained and integrated using partial least squares (PLS). Integration of eighty-two metabolites and forty-five selected candidate genes using PLS successfully differentiated 1-, 11-year-old E. longifolia roots and hairy root cultures, indicating significant metabolite-gene expression differences in response to different growth years and root types. Amino acids, 2-C-methyl-D-erythritol-4-phosphate cytidylyl-transferase (MCT) and acetyl-CoA C-acetyltransferase (AACT) were responsible for the discrimination of 1-year-old E. longifolia root. Quassinoids of eurycomanone and eurycomalactone and genes linked to the upstream synthesis in mevalonate (MVA) pathway contributed to the discrimination of the11-year-old E. longifolia root. 11-hydroxycanthin-6-one and genes that participate in the methylerythritol phosphate (MEP) pathway upstream of terpenoid biosynthesis were responsible for the discrimination of E. longifolia hairy root cultures. [ABSTRACT FROM AUTHOR]

Chaga mushroom (Inonotus obliquus) is a pathogenic fungus that grows mostly on birch species (Betula pendula Roth and B. pubescens Ehrh.) and has traditionally been used as an anticancer medicine. This study aimed to compare the chemical composition and cytotoxic activity of chagas growing on both Betula spp. on various cancer cell lines. The freeze-dried extracts contained triterpenes inotodiol, lanosterol betulin, and betulinic acid typical to conks growing on Betula species. The cytotoxic activity of chaga growing on Betula pendula and B. pubescens 80% ethanolic extracts against 31 human cancer cell lines was evaluated by a sulforhodamine B assay. Chaga extract showed moderate activity against all cancer cell lines examined; it did not result in high cytotoxicity (IC50 ≤ 20 µg/mL). The strongest inhibitions were observed with chaga (growing on B. pendula) extract on the HepG2 and CAL-62 cell line and with chaga (from B. pubescens) extract on the HepG2 cell line, with IC50 values of 37.71, 43.30, and 49.99 μg/mL, respectively. The chaga extracts from B. pendula exert somewhat stronger effects on most cancer cell lines studied than B. pubescens extracts, which can be attributed to a higher content of inotodiol in B. pendula extracts. This study highlights the potential of chaga as a source of bioactive compounds with selective anticancer properties. To the best of our knowledge, this study is the first investigation of the chemical composition of I. obliquus parasitizing on B. pubescens. [ABSTRACT FROM AUTHOR]

Aralia continentalis Kitag. (A. continentalis) holds significant medicinal value among the Aralia genus. It has traditionally been employed in ethnomedicine to address a wide range of conditions, including wind–cold–dampness arthralgia; rheumatic pain in the waist and lower extremities; lumbar muscular strain; injuries resulting from falls, fractures, contusions, and strains; headache; toothache; and abscesses. Modern pharmacological research has validated its therapeutic potential, encompassing anti-inflammatory, analgesic, antioxidant, antimicrobial, insecticidal, hepatoprotective, anti-diabetic, and cytotoxic properties, among other pharmacological effects. To compile comprehensive knowledge on A. continentalis, a rigorous literature search was undertaken utilizing databases like SciFinder, PubMed, and Web of Science. This review seeks to delve into the plant's traditional applications, geographical distribution, botanical characteristics, phytochemistry, and pharmacology. The objective is to lay a foundation and propose novel research directions for exploring the plant's potential applications. Currently, one hundred and fifty-nine compounds have been isolated and identified from A. continentalis, encompassing diterpenoids, steroids, triterpenoids, volatile components, phenolics, vitamins, trace elements, and other compounds. Notably, diterpenoids, steroids, triterpenoids, volatile components, and phenolics have exhibited pronounced pharmacological effects, such as anti-inflammatory, analgesic, antioxidant, hepatoprotective, antidiabetic, and antimicrobial activities. However, despite the extensive research conducted, further studies are imperative to unravel new components and mechanisms of action, necessitating more in-depth investigations. This comprehensive exploration could pave the way for advancing and harnessing the potential of A. continentalis. [ABSTRACT FROM AUTHOR]

Liquid state fermentation is now a commonly used route to obtain triterpenoids from Antrodia cinnamomea, and linolenic acid can significantly promote triterpenoids synthesis, whereas its action mechanism has not been studied. Here, we comprehensively performed an investigation on the mechanism of linolenic acid to promote triterpenoids production in liquid‐state fermentation of A. cinnamomea. Results showed that the addition of linolenic acid increased the unsaturated fatty acid index, fluidity, and permeability in the cell membrane of A. cinnamomea mycelia, favored the absorption of nutrients in the medium by the mycelium, enhanced the material exchange inside and outside, and thus promoted mycelial growth and triterpenoids synthesis. Moreover, 767 significantly differentially expressed genes were detected by adding linolenic acid, including 212 upregulated genes and 555 downregulated genes. The upregulated genes were mainly enriched in metabolism, glycolytic pathway, TCA cycle, and pyruvate metabolism. It was seen that the addition of linolenic acid improved the cell metabolic activity and promoted the synthesis of secondary metabolites, proving that the addition of linolenic acid improved the metabolic viability of cells and promoted secondary metabolite synthesis. [ABSTRACT FROM AUTHOR]

Objectives: Engelhardia roxburghiana Wall is a plant of the Juglandaceae family, and its leaves is the main part used as a medicine. It is used to relieve heat and pain, gasification, and dampness. The purpose of this review is to provide a systematic review about the botany, traditional uses, phytochemistry, pharmacology, and toxicology of this plant. Key findings: Many compounds have been isolated and identified from the plant, including flavonoids, triterpenoids, steroids, quinones, essential oils, and other types of chemical constituents. Extensive pharmacological activities of the extracts or compounds of E. roxburghiana Wall in vivo and in vitro were mainly confirmed, including anti-cancer, anti-diabetic, anti-inflammatory, and anti-allergic effects. Summary: In this paper, the botany, traditional uses, phytochemistry, and pharmacology of E. roxburghiana Wall were reviewed. In the future, E. roxburghiana Wall needs further study, such as paying more attention to quality control and the utilization on agriculture. In addition, discussing the medicinal components of decoction as well as the toxicity will also contribute to the progress of clinical trial studies. [ABSTRACT FROM AUTHOR]

The discovery of lupeol, a triterpenoid compound (C30H50O), in the ethyl acetate leaf extract of Justicia secunda (Blood root), has opened doors to extensive research and development opportunities in natural product-based pharmaceuticals. Lupeol’s versatile pharmacological properties, including anti-inflammatory, anticancer, antidiabetic, and antiviral effects, make it a compelling candidate for drug development. To fully harness its potential, a comprehensive understanding of lupeol’s structural and chemical attributes is crucial. Through quantum chemical calculations using the GAUSSIAN 09 suite of programs, we determined the optimized geometry, IR frequencies, bond distances (R), bond angles (A), dipole moments, HOMO-LUMO and other molecular parameters for this solitary molecule. The remarkable accuracy and reliability of computational techniques in predicting the properties of systems and reactants are evident in the consistently favorable results. A strong concordance and consistency between the experimental and computational outcomes further reinforces the credibility of our findings. This study offers a means to explore lupeol’s molecular behavior, providing insights that can guide future drug development efforts rooted in this promising natural compound. [ABSTRACT FROM AUTHOR]

Cancer is a global health problem, with the incidence rate estimated to reach 40% of the population by 2030. Although there are currently several therapeutic methods, none of them guarantee complete healing. Plant-derived natural products show high therapeutic potential in the management of various types of cancer, with some of them already being used in current practice. Among different classes of phytocompounds, pentacyclic triterpenoids have been in the spotlight of research on this topic. Ursolic acid (UA) and its structural isomer, oleanolic acid (OA), represent compounds intensively studied and tested in vitro and in vivo for their anticancer and chemopreventive properties. Since natural compounds can rarely be used in practice as such due to their characteristic physico-chemical properties, to tackle this problem, their derivatization has been attempted, obtaining compounds with improved solubility, absorption, stability, effectiveness, and reduced toxicity. This review presents various UA and OA derivatives that have been synthesized and evaluated in recent studies for their anticancer potential. It can be observed that the most frequent structural transformations were carried out at the C-3, C-28, or both positions simultaneously. It has been demonstrated that conjugation with heterocycles or cinnamic acid, derivatization as hydrazide, or transforming OH groups into esters or amides increases anticancer efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Centella is an important genus in the Apiaceae family. It includes Centella asiatica, which has significant edible and medicinal values. However, this species is easily confused due to its similar morphological traits to Hydrocotyle umbellata, hindering its utilization in the consumer and pharmacological industries. Objective: The study aims to differentiate these two closely related plant species using reliable methods of confirming the authenticity of natural herbal medicines. Methods: Our work mainly focuses on the basic morphological characteristics, chemical markers, genetic fingerprints, and their biological responses. Results: The plants can be clearly differentiated using their leaf shapes, stipules, petioles, inflorescences, and fruit structures. Although the phytochemical compositions of the C. asiatica extract were similar to that of H. umbellata which included flavonoids, tannins, and saponins important to the plant's ability to reduce inflammation and promote healing of wounds, the H. umbellata extract showed significantly higher toxicity than that of C. asiatica. High‐performance liquid chromatography analysis was used to identify chemical fingerprints. The result revealed that C. asiatica had major triterpene glycoside constituents including asiaticoside, asiatic acid, madecassoside, and madecassic acid, which have a wide range of medicinal values. In contrast, triterpenoid saponins were not identified in H. umbellata. Furthermore, using SCoT1–6 primers was possible to effectively and sufficiently created a dendrogram which successfully identified the closeness of the plants and confirmed the differences between the two plant species. Conclusion: Therefore, differentiation can be achieved through the combination of morphometrics, molecular bioactivity, and chemical analysis. Centella asiatica (L.) Urban and Hydrocotyle umbellata Linn are easily confused due to their similar morphological characteristics and habitats. Leaf shape, flower, and fruit characteristics are morphological markers to differentiate them. HPLC and SCoT markers are powerful tools to differentiate closely related plant species. C. asiatica had major triterpene glycoside constituents. They exhibit promising properties for anti‐inflammation and wound healing. The high toxicity of H. umbellata extract, however, raises serious concerns about its use in food, medicine, and cosmeceutical. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent type of cancer, the fifth leading cause of cancer-related deaths, and the second leading cause of cancer deaths among women globally. Recent research has provided increasing support for the significance of phytochemicals, both dietary and non-dietary, particularly triterpenoids, in the mitigation and management of breast cancer. Recent studies showed that triterpenoids are promising agents in the treatment and inhibition of breast cancer achieved through the implementation of several molecular modes of action on breast cancer cells. This review discusses recent innovations in plant triterpenoids and their underlying mechanisms of action in combating breast cancer within the timeframe spanning from 2017 to 2023. The present work is an overview of different plant triterpenoids with significant inhibition on proliferation, migration, apoptosis resistance, tumor angiogenesis, or metastasis in various breast cancer cells. The anticancer impact of triterpenoids may be attributed to their antiproliferative activity interfering with angiogenesis and differentiation, regulation of apoptosis, DNA polymerase inhibition, change in signal transductions, and impeding metastasis. The present review focuses on several targets, mechanisms, and pathways associated with pentacyclic triterpenoids, which are responsible for their anticancer effects. We could conclude that natural triterpenoids are considered promising agents to conquer breast cancer. [ABSTRACT FROM AUTHOR]

In the quest for bioactive compounds from Ganoderma, artificially cultivated fruiting bodies of Ganoderma cf. mastoporum, strain TBRC-BCC 47851 were chemically investigated. The study led to the isolation of three undescribed lanostane triterpenoids (1–3) together with twelve known compounds. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. The new compounds were inactive in the antimalarial and antitubercular activity assays. [ABSTRACT FROM AUTHOR]

Two new serratene triterpenes, 14α,21β-dihydroxyserrat-3β-yl acetate and 3α,21β-dihydroxyserrat-14-en-23-oic acid, together with eight known compounds were isolated from two club moss cultivars, Phlegmariurus carinatus (Desv.) Ching and Phlegmariurus nummulariifolius (Blume) Ching. 14α,21β- D dihydroxyserrat-3β-yl acetate (1) was isolated from P. carinatus, and 3α,21β-dihydroxyserrat-14-en-23-oic acid (2), an undescribed carboxylic group at C-23 position of the serratene triterpenoids, was isolated from P. nummulariifolius. The structures of these new compounds were elucidated by using HR-ESIMS, UV, IR, 1D (1H and 13C NMR spectra), 2D NMR spectra, experimental ECD spectrometry and the single-crystal X-ray analysis. Biological evaluation of 14α,21β-dihydroxyserrat-3β-yl acetate (1) and lycoclavanol (8) revealed moderate cytotoxic activity on three tumor cell lines (HepG2, A549 and HuCCA-1) whereas 3α,21β-dihydroxyserrat-14-en-23-oic acid (2) showed strong inhibitory effect on HuCCA-1 cells with the IC50 of 4.72 µM. [ABSTRACT FROM AUTHOR]

SUMMARY Triterpenoids (C30‐isoprenoids) represent a major group of natural products with various physiological functions in plants. Triterpenoids and their derivatives have medicinal uses owing to diverse bioactivities. Arjuna (Terminalia arjuna) tree bark accumulates highly oxygenated β‐amyrin‐derived oleanane triterpenoids (e.g., arjunic acid, arjungenin, and arjunolic acid) with cardioprotective roles. However, biosynthetic routes and enzymes remain poorly understood. We mined the arjuna transcriptome and conducted cytochrome P450 monooxygenase (P450) assays using Saccharomyces cerevisiae and Nicotiana benthamiana to identify six P450s and two P450 reductases for oxidative modifications of oleanane triterpenoids. P450 assays using oleananes revealed a greater substrate promiscuity of C‐2α and C‐23 hydroxylases/oxidases than C‐28 oxidases. CYP716A233 and CYP716A432 catalyzed β‐amyrin/erythrodiol C‐28 oxidation to produce oleanolic acid. C‐2α hydroxylases (CYP716C88 and CYP716C89) converted oleanolic acid and hederagenin to maslinic acid and arjunolic acid. CYP716C89 also hydroxylated erythrodiol and oleanolic aldehyde. However, CYP714E107a and CYP714E107b catalyzed oleanolic acid/maslinic acid/arjunic acid, C‐23 hydroxylation to form hederagenin, arjunolic acid and arjungenin, and hederagenin C‐23 oxidation to produce gypsogenic acid, but at a lower rate than oleanolic acid C‐23 hydroxylation. Overall, P450 substrate selectivity suggested that C‐28 oxidation is the first P450‐catalyzed oxidative modification in the arjuna triterpenoid pathway. However, the pathway might branch thereafter through C‐2α/C‐23 hydroxylation of oleanolic acid. Taken together, these results provided new insights into substrate range of P450s and unraveled biosynthetic routes of triterpenoids in arjuna. Moreover, complete elucidation and reconstruction of arjunolic acid pathway in S. cerevisiae and N. benthamiana suggested the utility of arjuna P450s in heterologous production of cardioprotective compounds. [ABSTRACT FROM AUTHOR]

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Dysoxyllum binectariferum is an important medicinal plant known for various biological activities like anti-inflammatory, CNS depressants, contraceptive, analgesic, immunomodulatory, antimalarial, antifeedant, leishmanicidal and antiviral. It is a rich source of rohitukine, a basic skeleton of flavopiridol. Phytochemical investigation of chloroform extracts of Dysoxyllum binectariferum leaves, lead to the isolation of beddomeilactone (1) and two new cycloartane type triterpenoids beddomeilactol (2) and binectarilactone-A (3) with modified A ring. Compounds were assessed for their in-vitro α-glucosidase inhibitory activity. Compound 1 was found to be most potent, showing IC50 of 17.99 ± 0.26 µg/ml which is comparable to the positive control acarbose. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Apples are among the most nutritionally valuable fruits and have a history of use in traditional Chinese medicine. Triterpenoids, the primary bioactive compounds found in apples, demonstrate significant antitumor activity.Following enrichment and optimization, the total content of major triterpenoids in total triterpenoids from apple peels (ATT) reached 5.76 g kg−1. The growth of MDA‐MB‐231 xenograft tumors was significantly inhibited after treatment with ATT. Network pharmacology analysis conclusively identified a close association between the antitumor effect of ATT and the phosphatidylinositol 3‐kinase–protein kinase B (PI3K‐Akt) signaling pathway. Experimental validation using MDA‐MB‐231 cells and a xenograft nude mouse model confirmed that ATT suppressed tumor cell proliferation effectively by modulating the PI3K‐Akt signaling pathway, which was consistent with the findings from network pharmacology. The total triterpenoids from apple peels also induced cell apoptosis by mediating the PI3K‐Akt signaling pathway.The total triterpenoids from apple peels can inhibit tumor cell proliferation and induce cell apoptosis effectively through the PI3K‐Akt signaling pathway, suggesting that ATT holds promise as a prospective therapeutic agent for breast cancer treatment. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Bioactive compounds have drawn much attention according to their various health benefits. However, poor dissolvability, low stability and limited bioavailability largely narrow their applications. Although a variety of nontoxic ingredients have been rapidly developed as vehicles to deliver bioactive compounds in the last few years, most of them are non-bioactive. Pentacyclic triterpenoids, owing to their unique self-assembly and co-assembly behaviors and different physiological functions, can construct bioactive carriers due to their higher biodegradability, biocompatibility and lower toxicity. In this paper, the basic classification, biological activities and physicochemical properties of pentacyclic triterpenoids were summarized. Additionally, applications of self-assembled and co-assembled pentacyclic triterpenoids as bioactive delivery systems to load bioactive components and future research directions were discussed. This study emphasizes the potential of pentacyclic triterpenoids as bioactive delivery systems, offering a new perspective for constructing self- or co-assemblies for further synergetic biological applications. [ABSTRACT FROM AUTHOR]

Background: Dengue fever has become a significant worldwide health concern, because of its high morbidity rate and the potential for an increase in mortality rates due to lack of adequate treatment. There is an immediate need for the development of effective medication for dengue fever. Methods: Homology modeling of dengue virus (DENV) non-structural 4B (NS4B) protein was performed by SWISS-MODEL to predict the 3D structure of the protein. Structure validation was conducted using PROSA, PROCHECK, Ramachandran plot, and VERIFY-3D. MOE software was used to find out the in-Silico inhibitory potential of the five triterpenoids against the DENV-NS4B protein. Results: The SWISS-MODEL was employed to predict the three-dimensional protein structure of the NS4B protein. Through molecular docking, it was found that the chosen triterpenoid NS4B protein had a high binding affinity interaction. It was observed that the NS4B protein binding energy for 15-oxoursolic acid, betulinic acid, ursolic acid, lupeol, and 3-o-acetylursolic acid were − 7.18, − 7.02, − 5.71, − 6.67 and − 8.00 kcal/mol, respectively. Conclusions: NS4B protein could be a promising target which showed good interaction with tested triterpenoids which can be developed as a potential antiviral drug for controlling dengue virus pathogenesis by inhibiting viral replication. However, further investigations are necessary to validate and confirm their efficacy. [ABSTRACT FROM AUTHOR]

AbstractTwo 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. [ABSTRACT FROM AUTHOR]

Background: Oleanolic acid (OA), a pentacyclic triterpenoid exhibiting specific anti-cancer properties and highly effective antioxidant activity, was isolated from traditional Chinese medicinal herbs. Conversely, the OA that impacts colon cancer (CC) cells and its underlying mechanisms remain poorly understood. Methods: The cytotoxic effect of OA alone or OA-5-Fluorouracil (5-FU) combination on normal and CC cells was analyzed by methyl thiazolyl diphenyl-tetrazolium bromide (MTT). Then, the impact of OA on CC cell lines (LoVo and HT-29) proliferation and stemness were measured using colon formation and tumorsphere formation assays. Octamerbinding transcription factor 4 (Oct4), Prominin-1 (CD133), Nanog, and transcription factor SOX-2 (SOX2) are cell stemness-related indicators whose expression was assessed using fluorescence qPCR assay, Western blotting, and immunohistochemistry. The effect of OA on the proliferative potency of CC cells was evaluated using an in vivo model. Results: The stem-like characteristics and clone production of colon cancer cells were markedly reduced by OA alone or in combination with OA-5-FU. Moreover, OA increases the susceptibility of CC cells to 5-FU by blocking the cell stemness-related markers (CD133, Nanog, SOX2, and Oct4) expression levels both in vitro and in vivo, as well as by inactivating the activator of transcription 3 (STAT3 signaling) and Janus kinase 2/signal transducer (JAK2). Conclusion: These findings imply that oleanolic acid, both in vitro and in vivo, suppresses the JAK2/STAT3 pathway, which in turn reverses chemoresistance and decreases colon cancer cell stemness. Therefore, by reducing the recommended amount of 5-FU, this strategy may improve chemotherapeutic effectiveness and minimize undesired side effects. [ABSTRACT FROM AUTHOR]

Oleanolic acid (OA) is a vegetable chemical that is present naturally in a number of edible and medicinal botanicals. It has been extensively studied by medicinal chemists and scientific researchers due to its biological activity against a wide range of diseases. A significant number of researchers have synthesized a variety of analogues of OA by modifying its structure with the intention of creating more potent biological agents and improving its pharmaceutical properties. In recent years, chemical and enzymatic techniques have been employed extensively to investigate and modify the chemical structure of OA. This review presents recent advancements in medical chemistry for the structural modification of OA, with a special focus on the biotransformation, semi-synthesis and relationship between the modified structures and their biopharmaceutical properties. [ABSTRACT FROM AUTHOR]

Panax notoginseng is a highly valued perennial medicinal herb in China and is widely used in clinical treatments. The main purpose of this study was to elucidate the changes in the composition of P. notoginseng saponins (PNSs), which are the main bioactive substances, triggered by arbuscular mycorrhizal fungi (AMF) via ultrahigh-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC–ESI–MS/MS). A total of 202 putative terpenoid metabolites were detected, of which 150 triterpene glycosides were identified, accounting for 74.26% of the total. Correlation analysis, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS–DA) of the metabolites revealed that the samples treated with AMF (group Ce) could be clearly separated from the CK samples. In total, 49 differential terpene metabolites were identified between the Ce and CK groups, of which 38 and 11 metabolites were upregulated and downregulated, respectively, and most of the upregulated differentially abundant metabolites were mainly triterpene glycosides. The relative abundances of the two major notoginsenosides (MNs), ginsenosides Rd and Re, and 13 rare notoginsenosides (RNs), significantly increased. The differential saponins, especially RNs, were more easily clustered into one branch and had a high positive correlation. It could be concluded that the biosynthesis and accumulation of some RNs share the same pathways as those triggered by AMF. This study provides a new way to obtain more notoginsenoside resources, particularly RNs, and sheds new light on the scientization and rationalization of the use of AMF agents in the ecological planting of medicinal plants. [ABSTRACT FROM AUTHOR]

Six lupane triterpenoids (1–6), including an undescribed one, 3,23-di-O-isopropylidene-lup-20(29)-ene (1), along with two oleane triterpenoids (7, 8), were isolated from the Zhuang ethnic medicinal plant Glochidion eriocarpum. Their structures were identified based on comprehensive NMR, MS, and physiochemical data analysis. Compounds 2, 7, and 8 significantly inhibited the production of nitride oxide (NO) of the LPS-induced RAW 264.7 cells, which may be attributed to the anti-inflammatory activity of this plant. [ABSTRACT FROM AUTHOR]

The Cycolcarya paliurus (C. paliurus) has a long history of medicinal use as a traditional Chinese medicine to deal with diabetic, hyperlipidemic, inflammatory, and cancer, and triterpenes are one of its main active substances. Current studies on triterpenoids from C. paliurus have shown that different combinations of extraction methods and techniques have been used to isolate triterpenes from the leaves of the tree. The structures of the isolated triterpenoids from C. paliurus have also been elucidated to analyze their biological activities and conformational relationships. This paper presents a comprehensive evaluation of the triterpenes in C. paliurus in terms of extraction and purification methods, chemical structure, active functions and utilization, in order to provide a reference for the further development and utilization of triterpenoids in C. paliurus. [ABSTRACT FROM AUTHOR]

Phytochemical study on 90% ethanol extract from the green walnut husks of Juglans mandshurica Maxim. resulted into the isolation of three undescribed triterpenoids, juglansmanoids A–C (1–3). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated components were evaluated in vitro for anti-hyaluronidase activities. As a result, triterpenoid 1 exhibited potent anti-hyaluronidase activity (IC50 = 9.78 μg/ml) three times more than the positive control drug oleanolic acid (IC50 = 40.12 μg/ml). [ABSTRACT FROM AUTHOR]

The X-ray crystal structure data of 12-α-fluoro-3β-hy­droxy­olean-28,13β-olide methanol hemisolvate, 2C30H47FO3·CH3OH, (1), and 12-α-fluoro-3β-hy­droxy­taraxer-28,14β-olide methanol hemisolvate, 2C30H47FO3·CH3OH, (2), are described. The fluoro­lactonization of oleanolic acid using SelectfluorTM yielded a mixture of the six-membered δ-lactone (1) and the unusual seven-membered γ-lactone (2) following a 1,2-shift of methyl C-27 from C-14 to C-13. [ABSTRACT FROM AUTHOR]

By modifying ring A in the dammarane triterpenoid dipterocarpol, derivatives with isoxazole and 2-cyano-1-ene fragments were synthesized, which showed activity against the influenza A virus (H1N1) with selectivity indices of 19 and 23. [ABSTRACT FROM AUTHOR]

A critical overview of the separation of three relevant triterpenic acids, namely betulinic, oleanolic, and ursolic acids, by liquid and supercritical fluid chromatography is presented in this review. These triterpenic acids are commonly found in different biomass residues and have raised great research attention in recent years due to their broad and valuable therapeutic properties. Accordingly, fundamental aspects such as solubilities in single and mixed solvents, commercial stationary phases (octadecylsilyl and other bonded phases like triacontylsilyl, as well as porous graphitic columns), custom adsorbents (molecularly imprinted polymers and other polymeric adsorbents), mobile phases (conventional HPLC solvents and super/subcritical fluids), mobile-phase modifiers (acidic, basic, and cyclodextrins), pre-column derivatization strategies, and influence of temperature have been compiled, analyzed and thoroughly discussed in terms of (calculated) separation selectivities, peaks resolution, orders of elution, systems descriptors, etc. The most relevant achievements and gaps in this area of research are highlighted, together with a final comparison of the separation performance of the chromatographic systems reported in the literature. [ABSTRACT FROM AUTHOR]

Triterpenoid is a group of natural products with various remarkable activities, including cytotoxic. One of the sources for this type of compounds is Swietenia genus belong to Meliaceae family. This genus known to contains various secondary metabolites including limonoids, flavonoids, and triterpenoids. Especially for triterpenoid, there is limited report on isolation as well as biological activity from Swietenia genus, such as Swietenia mahagoni. In this research, three triterpenoid compounds have been successively isolated and identified from n-hexane extract, namely, (-)-leucophyllone (1), toonaciliatavarin E (2), and moronic acid (3). All isolated were assed against MCF-7 breast cancer and CV-1 normal kidney cell lines. The result showed that only moronic acid (3) performed moderate activity against two cells with IC50 of 63.10 and 48.04 µM, respectively. The other isolated compounds (1 and 2) showed weak cytotoxicity with IC50 > 500 µM. Based on preliminary structure activity relationship, revealed that pentacyclic triterpenoid (moronic acid, 3) showed stronger cytotoxicity compare with tetracyclic triterpenoids (-)-leucophyllone (1) and toonaciliatavarin E (2). [ABSTRACT FROM AUTHOR]

Yeast has been an indispensable host for synthesizing complex plant-derived natural compounds, yet the yields remained largely constrained. This limitation mainly arises from overlooking the importance of cell and pathway suitability during the optimization of enzymes and pathways. Herein, beyond conventional enzyme engineering, we dissected metabolic suitability with a framework for simultaneously augmenting cofactors and carbon flux to enhance the biosynthesis of heterogenous triterpenoids. We further developed phospholipid microenvironment engineering strategies, dramatically improving yeast's suitability for the high performance of endoplasmic reticulum (ER)-localized, rate-limiting plant P450s. Combining metabolic and microenvironment suitability by manipulating only three genes, NHMGR (NADH-dependent HMG-CoA reductase), SIP4 (a DNA-binding transcription factor)and GPP1 (Glycerol-1-phosphate phosphohydrolase 1), we enabled the high-level production of 4.92 g/L rare licorice triterpenoids derived from consecutive oxidation of β-amyrin by two P450 enzymes after fermentation optimization. This production holds substantial commercial value, highlighting the critical role of establishing cell suitability in enhancing triterpenoid biosynthesis and offering a versatile framework applicable to various plant natural product biosynthetic pathways.

The X-ray crystal structure data of 12-α-fluoro-3β-hydroxyolean-28,13β-olide methanol hemisolvate, 2C30H47FO3·CH3OH, (1), and 12-α-fluoro-3β-hydroxytaraxer-28,14β-olide methanol hemisolvate, 2C30H47FO3·CH3OH, (2), are described. The fluorolactonization of oleanolic acid using SelectfluorTM yielded a mixture of the six-membered δ-lactone (1) and the unusual seven-membered γ-lactone (2) following a 1,2-shift of methyl C-27 from C-14 to C-13.

Abstract Background Dengue fever has become a significant worldwide health concern, because of its high morbidity rate and the potential for an increase in mortality rates due to lack of adequate treatment. There is an immediate need for the development of effective medication for dengue fever. Methods Homology modeling of dengue virus (DENV) non-structural 4B (NS4B) protein was performed by SWISS-MODEL to predict the 3D structure of the protein. Structure validation was conducted using PROSA, PROCHECK, Ramachandran plot, and VERIFY-3D. MOE software was used to find out the in-Silico inhibitory potential of the five triterpenoids against the DENV-NS4B protein. Results The SWISS-MODEL was employed to predict the three-dimensional protein structure of the NS4B protein. Through molecular docking, it was found that the chosen triterpenoid NS4B protein had a high binding affinity interaction. It was observed that the NS4B protein binding energy for 15-oxoursolic acid, betulinic acid, ursolic acid, lupeol, and 3-o-acetylursolic acid were − 7.18, − 7.02, − 5.71, − 6.67 and − 8.00 kcal/mol, respectively. Conclusions NS4B protein could be a promising target which showed good interaction with tested triterpenoids which can be developed as a potential antiviral drug for controlling dengue virus pathogenesis by inhibiting viral replication. However, further investigations are necessary to validate and confirm their efficacy.

Ginseng, a cornerstone of traditional herbal medicine in Asia, garnered significant attention for its therapeutic potential. Central to its pharmacological effects are ginsenosides, the primary active metabolites, many of which fall within the dammarane-type and share protopanaxadiol as a common precursor. Challenges in extracting protopanaxadiol and ginsenosides from ginseng arise due to their low concentrations in the roots. Emerging solutions involve leveraging microbial cell factories employing genetically engineered yeasts. Here, we optimized the fermentation conditions via the Design of Experiment, realizing 1.2 g/L protopanaxadiol in simple shake flask cultivations. Extrapolating the optimized setup to complex ginsenosides, like compound K, achieved 7.3-fold (0.22 g/L) titer improvements. Our adaptable fermentation conditions enable the production of high-value products, such as sustainable triterpenoids synthesis. Through synthetic biology, microbial engineering, and formulation studies, we pave the way for a scalable and sustainable production of bioactive compounds from ginseng. [Display omitted] • Cultivation optimization to increase protopanaxadiol production above 1.2 g/L in a shake flask by engineered yeast. • The M3 medium also supported high production of other triterpenoids (lupeol-type and dammarane-type) by engineered yeasts. • The simple cultivation fosters clone screening and small-scale synthesis, paving the way for triterpenoids biosynthesis. [ABSTRACT FROM AUTHOR]

Neurological disorders including neurodegenerative disorders continue to pose significant therapeutic challenges. Triterpenoids, a diverse group of natural compounds found abundantly in plants, possess promising neuroprotective properties. This review aims to explore the potential of triterpenoids in mitigating neurodegeneration through various mechanisms, including antioxidant, anti-inflammatory, and anti-apoptotic activities. The neuroprotective potential of some notable triterpenoids, such as asiatic acid, asiaticoside, madecassoside, bacoside A, bacopaside I, ganoderic acids, and lucidenic acids are discussed in terms of their ability to modulate key pathways implicated in neurological disorders. Additionally, the potential therapeutic applications of triterpenoids in Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, spinal cord injury, and epilepsy are examined. Furthermore, the review also underlines the challenges for the development of triterpenoids as neuroprotective agents, including the need for further preclinical and clinical studies to elucidate their efficacy and safety for translation into clinical practice.

Abstract Background The burden of cancer incidences and mortality is rapidly increasing worldwide resulting in an increased demand for new therapies. Secondary metabolites extracted from medicinal plants have significantly contributed toward discovery of new cancer therapies some of which are in clinical use. In this study, anticancer potential of four triterpenoids, namely oleanonic acid (EK-2), 3-epi-oleanolic acid (EK-8), 1,2,3,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (EK-4) and 2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (EK-9), extracted from Ekebergia capensis Sparrm root bark was evaluated. Results We employed CLC-Pred to initially evaluate cytotoxicity of previously isolated compounds in silico where predictions revealed high probability of bioactivity. The compounds were then submitted to the National Cancer Institute (NCI), Developmental Therapeutics Program, for bioactivity evaluation against NCI-60 human tumor cell lines. The four compounds demonstrated a range of potencies at a concentration of 10 µM. The results revealed that EK-9 was the most potent with mean growth percent of 32.84 and cases of lethality (negative growth percent) against two leukemia cell lines (HL-60 (TB) and RPMI-8226) and HT29 (colon cancer) and SK-MEL-5 (melanoma). This molecule was further evaluated in a five-dose assay where notable growth inhibition against leukemia cells, HL-60 (TB), RPMI-8226 and K-562 was observed with growth inhibitory activity (GI50) values of 3.10, 3.74 and 5.07 µM, respectively. In addition, total growth inhibition was observed at 11.2 μM and 18.9 μM for HL-60 (TB) and RPMI-8226 cells, respectively, partly accounting for the negative growth percent. Conclusion The study has demonstrated anticancer properties of the four triterpenoids with compound EK-9 being the most potent overall having selective bioactivity in leukemia and breast cancer cells. Further studies focusing on elucidating its mechanism of action will be useful in exploration of the therapeutic potential of triterpenoids in general.

Rosa rugosa is highly regarded for its aesthetic and therapeutic qualities. In particular, R. rugosa's flowers are known to produce essential oils containing a mixture of volatile terpenes, phenylpropanoids, and other compounds. Despite this, extensive research exists on volatile terpenes in flowers, while the knowledge of non-volatile terpenes in distinct tissues is still limited. Using UPLC–ESI–MS/MS, a comprehensive analysis of the terpene metabolites in five different tissues of R. rugosa was conducted. These metabolites accumulated in distinct tissues, and the majority of them were triterpenoids. Transcriptome data were collected from five tissues using RNA-seq. Transcriptomics and metabolomics were utilized to evaluate the triterpene biosynthesis pathway, resulting in new insights into its regulation and biosynthesis. The RrOSC10 was identified as a key enzyme in converting 2,3-oxidosqualene into α-amyrin, potentially contributing to the triterpene biosynthesis pathway. Furthermore, the expression of the RrOSC10 gene was upregulated by salinity for 0.5 h and 1 h, with subsequent downregulation at 2 h. This study lays a foundation for future research on the biosynthesis and accumulation of triterpenes in R. rugosa. [ABSTRACT FROM AUTHOR]

Euphorbia serpens has been used in central-west region of Argentina in traditional medicine as diuretic plant. The aim of this present study was to evaluate the diuretic activity of E. serpens in-vivo. We used dried aerial parts, and infusions from these were orally administered to Wistar rats. Its effect was evaluated using furosemide as a positive drug and isotonic salt solution as negative control. Their urine output was quantified at several time intervals. The volume of urine excreted and Na+ increased significantly, being similar to furosemide. Mannitol, was the main component in aqueous extracts of E. serpens, and the acetone extract showed the presence of Δ12- oleanane-type triterpenoids compounds, mainly hederagenin. No toxic effects were observed. [ABSTRACT FROM AUTHOR]

Ovarian Cancer (OC) is a prevalent gynecological malignancy, underscoring the urgency to discover novel therapeutic approaches that enhance both clinical efficacy and safety. Taraxasterol (TA), an important component of dandelion, has been reported to exhibit inhibitory effects on the progression of various tumors. However, its specific role in OC is yet to be reported. In this present study, we observed that TA significantly inhibits the proliferation of OC cells, promotes apoptosis and reduces OC cell migration and angiogenesis. Mechanistically, TA targets the EPH receptor A2 (EphA2) receptor, thereby inhibiting OC progression. In conclusion, the ability of TA to suppress both cell proliferation and angiogenesis in OC through EphA2 targeting suggests its potential utility as a therapeutic agent for OC. [ABSTRACT FROM AUTHOR]

In our previous study, two oleanane-type pentacyclic triterpenoids (oleanolic acid and maslinic acid) were reported to affect the N-glycosylation and intracellular trafficking of intercellular adhesion molecule-1 (ICAM-1). The present study was aimed at investigating the structure–activity relationship of 13 oleanane-type natural triterpenoids with respect to the nuclear factor κB (NF-κB) signaling pathway and the expression, intracellular trafficking, and N-glycosylation of the ICAM-1 protein in human lung adenocarcinoma A549 cells. Hederagenin, echinocystic acid, erythrodiol, and maslinic acid, which all possess two hydroxyl groups, decreased the viability of A549 cells. Celastrol and pristimerin, both of which possess an α,β-unsaturated carbonyl group, decreased cell viability but more strongly inhibited the interleukin-1α-induced NF-κB signaling pathway. Oleanolic acid, moronic acid, and glycyrrhetinic acid interfered with N-glycosylation without affecting the cell surface expression of the ICAM-1 protein. In contrast, α-boswellic acid and maslinic acid interfered with the N-glycosylation of the ICAM-1 protein, which resulted in the accumulation of high-mannose-type N-glycans. Among the oleanane-type triterpenoids tested, α-boswellic acid and maslinic acid uniquely interfered with the intracellular trafficking and N-glycosylation of glycoproteins. [ABSTRACT FROM AUTHOR]

This research focuses on the target deconvolution of the natural compound myrianthic acid, a triterpenoid characterized by an ursane skeleton isolated from the roots of Myrianthus arboreus and from Oenothera maritima Nutt. (Onagraceae), using MS-based chemical proteomic techniques. Application of drug affinity responsive target stability (DARTS) and targeted-limited proteolysis coupled to mass spectrometry (t-LiP-MS) led to the identification of the enzyme fatty acid synthase (FAS) as an interesting macromolecular counterpart of myrianthic acid. This result, confirmed by comparison with the natural ursolic acid, was thoroughly investigated and validated in silico by molecular docking, which gave a precise picture of the interactions in the MA/FAS complex. Moreover, biological assays showcased the inhibitory activity of myrianthic acid against the FAS enzyme, most likely related to its antiproliferative activity towards tumor cells. Given the significance of FAS in specific pathologies, especially cancer, the myrianthic acid structural moieties could serve as a promising reference point to start the potential development of innovative approaches in therapy. [ABSTRACT FROM AUTHOR]

An unprescribed nortriterpenoid with an aromatic E ring, uncanortriterpenoid A (1), together with fourteen known triterpenoids (2–15), were isolated from the hook-bearing stems of Uncaria rhynchophylla Miq. Based on extensive spectroscopic analyses, the NMR data of 2, 5, and 10 in CD3OD were assigned for the first time, and the wrongly assigned δC of C-27 and C-29 of 2 were revised. Among the known compounds, 7, 13, and 15 were isolated from this species for the first time, and 15 represents the first lanostane triterpenoid bearing an extra methylidene at C-24 for the Rubiaceae family. Additionally, compounds 6 and 14 exhibited moderate ferroptosis inhibitory activity, with an EC50 value of 14.74 ± 0.20 μM for 6 and 23.11 ± 1.31 μM for 14. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and life-threatening lung disease for which treatment options are limited. Glycyrrhetinic acid (GA) is a triterpenoid with multiple biological effects, such as anti-inflammatory and anti-fibrotic properties. Herein, inhalable milk-derived extracellular vesicles (mEVs) encapsulating GA (mEVs@GA) were screened and evaluated for IPF treatment. The results indicated that the loading efficiency of GA in mEVs@GA was 8.65%. Therapeutic effects of inhalable mEVs@GA were investigated in vitro and in vivo. The mEVs@GA demonstrated superior anti-inflammatory effects on LPS-stimulated MHS cells. Furthermore, repeated noninvasive inhalation delivery of mEVs@GA in bleomycin-induced IPF mice could decrease the levels of transforming growth factors β1 (TGF-β1), Smad3 and inflammatory cytokines IL-6, IL-1β and TNF-α. The mEVs@GA effectively diminished the development of fibrosis and improved pulmonary function in the IPF mice model at a quarter of the dose compared with the pirfenidone oral administration group. Additionally, compared to pirfenidone-loaded mEVs, mEVs@GA demonstrated superior efficacy at the same drug concentration in the pharmacodynamic study. Overall, inhaled mEVs@GA have the potential to serve as an effective therapeutic option in the treatment of IPF. Glycyrrhetinic acid (GA)-loaded milk-derived extracellular vesicles (mEVs) were successfully constructed and inhaled by bleomycin-induced mice, resulting in successful improvement of idiopathic pulmonary fibrosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The burden of cancer incidences and mortality is rapidly increasing worldwide resulting in an increased demand for new therapies. Secondary metabolites extracted from medicinal plants have significantly contributed toward discovery of new cancer therapies some of which are in clinical use. In this study, anticancer potential of four triterpenoids, namely oleanonic acid (EK-2), 3-epi-oleanolic acid (EK-8), 1,2,3,22,23-pentahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (EK-4) and 2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene (EK-9), extracted from Ekebergia capensis Sparrm root bark was evaluated. Results: We employed CLC-Pred to initially evaluate cytotoxicity of previously isolated compounds in silico where predictions revealed high probability of bioactivity. The compounds were then submitted to the National Cancer Institute (NCI), Developmental Therapeutics Program, for bioactivity evaluation against NCI-60 human tumor cell lines. The four compounds demonstrated a range of potencies at a concentration of 10 µM. The results revealed that EK-9 was the most potent with mean growth percent of 32.84 and cases of lethality (negative growth percent) against two leukemia cell lines (HL-60 (TB) and RPMI-8226) and HT29 (colon cancer) and SK-MEL-5 (melanoma). This molecule was further evaluated in a five-dose assay where notable growth inhibition against leukemia cells, HL-60 (TB), RPMI-8226 and K-562 was observed with growth inhibitory activity (GI50) values of 3.10, 3.74 and 5.07 µM, respectively. In addition, total growth inhibition was observed at 11.2 μM and 18.9 μM for HL-60 (TB) and RPMI-8226 cells, respectively, partly accounting for the negative growth percent. Conclusion: The study has demonstrated anticancer properties of the four triterpenoids with compound EK-9 being the most potent overall having selective bioactivity in leukemia and breast cancer cells. Further studies focusing on elucidating its mechanism of action will be useful in exploration of the therapeutic potential of triterpenoids in general. [ABSTRACT FROM AUTHOR]

We previously conducted a systematic study on the metabolic process and products of hederasaponin B in rats. We hypothesized that the sugar chain structures play a key role in the metabolism of triterpenoid saponins. To verify this hypothesis, we conducted metabolic research on ciwujianoside B ascribed to the same sugar chains and a distinct aglycone and compared it with hederasaponin B. Specifically, we collected feces, urine, and plasma of rats after gavage with ciwujianoside B and identified 42 metabolites by UPLC-Fusion Lumos Orbitrap mass spectrometry. Finally, ciwujianoside B metabolism and hederasaponin B metabolism were compared, reaching the following conclusions: (i) more than 40 metabolites were identified in both, with the majority of metabolites identified in feces; (ii) the corresponding metabolic pathways in vivo were basically similar, including deglycosylation, acetylation, hydroxylation, glucuronidation, oxidation, and glycosylation; and (iii) deglycosylation was considered the main metabolic reaction, and its metabolites accounted for approximately 50% of all metabolites. Overall, this study provides a foundation for further research on the metabolism of triterpenoid saponins. [ABSTRACT FROM AUTHOR]

Gynostemma pentaphyllum (Thunb.) Makino is an important producer of dammarene-type triterpenoid saponins. These saponins (gypenosides) exhibit diverse pharmacological benefits such as anticancer, antidiabetic, and immunomodulatory effects, and have major potential in the pharmaceutical and health care industries. Here, we employed single-cell RNA sequencing (scRNA-seq) to profile the transcriptomes of more than 50,000 cells derived from G. pentaphyllum shoot apexes and leaves. Following cell clustering and annotation, we identified five major cell types in shoot apexes and four in leaves. Each cell type displayed substantial transcriptomic heterogeneity both within and between tissues. Examining gene expression patterns across various cell types revealed that gypenoside biosynthesis predominantly occurred in mesophyll cells, with heightened activity observed in shoot apexes compared to leaves. Furthermore, we explored the impact of transposable elements (TEs) on G. pentaphyllum transcriptomic landscapes. Our findings the highlighted the unbalanced expression of certain TE families across different cell types in shoot apexes and leaves, marking the first investigation of TE expression at the single-cell level in plants. Additionally, we observed dynamic expression of genes involved in gypenoside biosynthesis and specific TE families during epidermal and vascular cell development. The involvement of TE expression in regulating cell differentiation and gypenoside biosynthesis warrant further exploration. Overall, this study not only provides new insights into the spatiotemporal organization of gypenoside biosynthesis and TE activity in G. pentaphyllum shoot apexes and leaves but also offers valuable cellular and genetic resources for a deeper understanding of developmental and physiological processes at singlecell resolution in this species. [ABSTRACT FROM AUTHOR]

In this study, we report the mutational profiles, pathogenicity, and their association with different clinicopathologic and sociogenetic factors in patients with Pashtun ethnicity for the first time. A total of 19 FFPE blocks of invasive ductal carcinoma (IDC) from the Breast Cancer (BC) tissue and 6 normal FFPE blocks were analyzed by whole-exome sequencing (WES). Various somatic and germline mutations were identified in cancer-related genes, i.e., ATM, CHEK2, PALB2, and XRCC2. Among a total of 18 mutations, 14 mutations were somatic and 4 were germline. The ATM gene exhibited the maximum number of mutations (11/18), followed by CHEK2 (3/18), PALB2 (3/18), and XRCC2 (1/18). Except one frameshift deletion, all other 17 mutations were nonsynonymous single-nucleotide variants (SNVs). SIFT prediction revealed 7/18 (38.8%) mutations as deleterious. PolyPhen-2 and MutationTaster identified 5/18 (27.7%) mutations as probably damaging and 10/18 (55.5%) mutations as disease-causing, respectively. Mutations like PALB2 p.Q559R (6/19; 31.5%), XRCC2 p.R188H (5/19; 26.31%), and ATM p.D1853N (4/19; 21.05%) were recurrent mutations and proposed to have a biomarker potential. The protein network prediction was performed using GeneMANIA and STRING. ISPRED-SEQ indicated three interaction site mutations which were further used for molecular dynamic simulation. An average increase in the radius of gyration was observed in all three mutated proteins revealing their perturbed folding behavior. Obtained SNVs were further correlated with various parameters related to the clinicopathological status of the tumors. Three mutation positions (ATM p. D1853N, CHEK2 p.M314I, and PALB2 p.T1029S) were found to be highly conserved. Finally, the wild- and mutant-type proteins were screened for two drugs: elagolix (DrugBank ID: DB11979) and LTS0102038 (a triterpenoid, isolated from the anticancer medicinal plant Fagonia indica). Comparatively, a higher number of interactions were noted for normal ATM with both compounds, as compared to mutants. [ABSTRACT FROM AUTHOR]