Lignans from the seeds of Herpetospermum pedunculosum and their farnesoid X receptor-activating effect

Meng, Fan-Cheng; Ma, Yingxiong; Zhan, Honghong; Zong, Wei; Linghu, Lang; Wang, Zhe; Lan, Xiaozhong; Liao, Zhihua; Chen, Min

doi:10.1016/j.phytochem.2021.113010

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…In higher plants, the biosynthesis of lignans is not only controlled by genes that are connected to catalytic processes but also involves a multitude of transcription factors. Several transcription factors, such as bHLH44, NAC54, MYB18, TNY, and EBP are involved in the regulation of lignan accumulation in Isatis indigotica [ 26 , 34 ]. According to the TF-lignan-related metabolite network analysis, HSFB3 was highly correlated with all selected phenylpropanoid and lignan pathway DEMs (five upregulated and two downregulated), except for secoisolariciresinol (Fig.…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae)

Zhu,

Chen,

Sun

et al. 2024

BMC Genomics

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Background Herpetospermum pedunculosum (Ser.) C. B. Clarke is a traditional Chinese herbal medicine that heavily relies on the lignans found in its dried ripe seeds (Herpetospermum caudigerum), which have antioxidant and hepatoprotective functions. However, little is known regarding the lignan biosynthesis in H. pedunculosum. In this study, we used metabolomic (non-targeted UHPLC-MS/MS) and transcriptome (RNA-Seq) analyses to identify key metabolites and genes (both structural and regulatory) associated with lignan production during the green mature (GM) and yellow mature (YM) stages of H. pedunculosum. Results The contents of 26 lignan-related metabolites and the expression of 30 genes involved in the lignan pathway differed considerably between the GM and YM stages; most of them were more highly expressed in YM than in GM. UPLC-Q-TOF/MS confirmed that three Herpetospermum-specific lignans (including herpetrione, herpetotriol, and herpetin) were found in YM, but were not detected in GM. In addition, we proposed a lignan biosynthesis pathway for H. pedunculosum based on the fundamental principles of chemistry and biosynthesis. An integrated study of the transcriptome and metabolome identified several transcription factors, including HpGAF1, HpHSFB3, and HpWOX1, that were highly correlated with the metabolism of lignan compounds during seed ripening. Furthermore, functional validation assays revealed that the enzyme 4-Coumarate: CoA ligase (4CL) catalyzes the synthesis of hydroxycinnamate CoA esters. Conclusion These results will deepen our understanding of seed lignan biosynthesis and establish a theoretical basis for molecular breeding of H. pedunculosum.

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Section: Discussionmentioning

confidence: 99%

Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae)

Zhu,

Chen,

Sun

et al. 2024

BMC Genomics

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“…Another feature of NASH is the manifestation of liver inflammation, which is believed to contribute to the formation of fibrosis [ 32 ]. Previous studies have shown that H. caudigerum contains lignan components that exhibit free radical-scavenging, antioxidant, and anti-inflammatory effects [ 33 , 34 ]. Moreover, research has shown that H. caudigerum is capable of reducing the MDA content in the liver, increasing the superoxide dismutase content, and inhibiting the expression of NF-κB.…”

Section: Discussionmentioning

confidence: 99%

Herpetrione, a New Type of PPARα Ligand as a Therapeutic Strategy Against Nonalcoholic Steatohepatitis

Linghu,

Zong,

Liao

et al. 2023

Research

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Non-alcoholic fatty liver disease, especially nonalcoholic steatohepatitis (NASH), is a leading cause of cirrhosis and liver cancer worldwide; nevertheless, there are no Food and Drug Administration-approved drugs for treating NASH until now. Peroxisome proliferator-activated receptor alpha (PPARα) is an interesting therapeutic target for treating metabolic disorders in the clinic, including NASH. Herpetrione, a natural lignan compound isolated from Tibetan medicine Herpetospermum caudigerum , exerts various hepatoprotective effects, but its efficacy and molecular mechanism in treating NASH have not yet been elucidated. Here, we discovered that herpetrione lessened lipid accumulation and inflammation in hepatocytes stimulated with oleic acid and lipopolysaccharide, and effectively alleviated NASH caused by a high-fat diet or methionine-choline-deficient diet by regulating glucolipid metabolism, insulin resistance, and inflammation. Mechanistically, RNA-sequencing analyses further showed that herpetrione activated PPAR signaling, which was validated by protein expression. Furthermore, the analysis of molecular interactions illustrated that herpetrione bound directly to the PPARα protein, with binding sites extending to the Arm III domain. PPARα deficiency also abrogated the protective effects of herpetrione against NASH, suggesting that herpetrione protects against hepatic steatosis and inflammation by activation of PPARα signaling, thereby alleviating NASH. Our findings shed light on the efficacy of a natural product for treating NASH, as well as the broader prospects for NASH treatment by targeting PPARα.

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“…Its dried mature seeds (HPS) known as "Se-ji-mei-duo" in Tibetan medicine (Yang, 1989), have been used for jaundice, hepatitis and dyspepsia treatment for decades. Early phytochemical studies revealed the presence of lignans (Kaouadji and Pieraccini, 1984;Dai et al, 2017), fatty acids (Zhao et al, 2009) and terpenes (Jiang et al, 2016) in HPS, conferring anti-inflammatory (Fang et al, 2007), anti-tumour (Teodor et al, 2020), anti-HBV (Gong et al, 2016), and hepatoprotective effects (Wang et al, 2014;Yu et al, 2014;Shen et al, 2015;Liu et al, 2017;Linghu et al, 2023). Our group reported the existence of series of lignans in HPS, which exhibited protection against CCl 4 -induced hepatic fibrosis (Feng et al, 2018;Li et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Total cucurbitacins from Herpetospermum pedunculosum pericarp do better than Hu-lu-su-pian (HLSP) in its safety and hepatoprotective efficacy

Liu,

Xu,

et al. 2024

Front. Pharmacol.

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The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.

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Lignans from the seeds of Herpetospermum pedunculosum and their farnesoid X receptor-activating effect

Cited by 5 publications

References 40 publications

Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae)

Integrative analysis of the metabolome and transcriptome provides insights into the mechanisms of lignan biosynthesis in Herpetospermum pedunculosum (Cucurbitaceae)

Herpetrione, a New Type of PPARα Ligand as a Therapeutic Strategy Against Nonalcoholic Steatohepatitis

Total cucurbitacins from Herpetospermum pedunculosum pericarp do better than Hu-lu-su-pian (HLSP) in its safety and hepatoprotective efficacy

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