Dehydrodiconiferyl alcohol, a lignan from Herpetospermum pedunculosum, alleviates cholestasis by activating pathways associated with the farnesoid X receptor

Wei, Xiaodong; Ma, Yingxiong; Dong, Zhaoyue; Wang, Guowei; Lan, Xiaozhong; Liao, Zhihua; Chen, Min

doi:10.1016/j.phymed.2020.153378

Cited by 19 publications

(7 citation statements)

References 32 publications

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“…To confirm its agonistic activity, knockdown of the expression of FXR in L-02 cells was performed. The mRNA and protein levels of FXR as well as a range of keys downstream has been remarkably upregulated after treatment with 205, which were decreased in Si-FXR cells ( Wei et al, 2021 ).…”

Section: Natural Products Targeting Farnesoid X Receptormentioning

confidence: 99%

Natural Products Targeting Liver X Receptors or Farnesoid X Receptor

She

Pang

et al. 2022

Front. Pharmacol.

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Nuclear receptors (NRs) are a superfamily of transcription factors induced by ligands and also function as integrators of hormonal and nutritional signals. Among NRs, the liver X receptors (LXRs) and farnesoid X receptor (FXR) have been of significance as targets for the treatment of metabolic syndrome-related diseases. In recent years, natural products targeting LXRs and FXR have received remarkable interests as a valuable source of novel ligands encompassing diverse chemical structures and bioactive properties. This review aims to survey natural products, originating from terrestrial plants and microorganisms, marine organisms, and marine-derived microorganisms, which could influence LXRs and FXR. In the recent two decades (2000–2020), 261 natural products were discovered from natural resources such as LXRs/FXR modulators, 109 agonists and 38 antagonists targeting LXRs, and 72 agonists and 55 antagonists targeting FXR. The docking evaluation of desired natural products targeted LXRs/FXR is finally discussed. This comprehensive overview will provide a reference for future study of novel LXRs and FXR agonists and antagonists to target human diseases, and attract an increasing number of professional scholars majoring in pharmacy and biology with more in-depth discussion.

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Section: Natural Products Targeting Farnesoid X Receptormentioning

confidence: 99%

Natural Products Targeting Liver X Receptors or Farnesoid X Receptor

She

Pang

et al. 2022

Front. Pharmacol.

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“…Transporters via Activating the Sirt1/FXR/ Nrf2 Pathway Documents are showing that FXR is a key regulator of NTCP, BSEP and MRP2 (Wei et al, 2021). Nrf2 regulates the expression of MRP3 and MRP4 (Cornejo et al, 2013).…”

Section: Ga Regulated the Expression Of Hepaticmentioning

confidence: 99%

Glycyrrhetinic Acid Protects α-Naphthylisothiocyanate- Induced Cholestasis Through Regulating Transporters, Inflammation and Apoptosis

et al. 2021

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Glycyrrhetinic acid (GA), the active metabolic product of Glycyrrhizin (GL) that is the main ingredient of licorice, was reported to protect against α-naphthylisothiocyanate (ANIT)- induced cholestasis. However, its protective mechanism remains unclear. In our work, the cholestatic liver injury in mice was caused by ANIT and GA was used for the treatment. We assessed cholestatic liver injury specific indexes, histopathological changes, bile acid transporters, inflammation and apoptosis. The results of liver biochemical index and histopathological examination showed that GA markedly attenuated ANIT-induced liver injury. Mechanism research suggested that GA could activate the expression of farnesoid x receptor (FXR) and its downstream bile acids transporters Na+/taurocholate co-transporting polypeptide (NTCP), bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2), as well as the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins MRP3, MRP4. These transporters play a vital role in mediating bile acid homeostasis in hepatocytes. Moreover, GA could significantly inhibit the ANIT-induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory pathway and the increase of tumor necrosis factor-α (TNF-α) concentration in serum. Also, GA protected against ANIT-induced mitochondrial apoptosis by regulating the expression of Bcl-2, Bax, cleaved caspase 3 and cleaved caspase 9. In conclusion, GA alleviates the hepatotoxicity caused by ANIT by regulating bile acids transporters, inflammation and apoptosis, which suggests that GA may be a potential therapeutic agent for cholestasis.

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“…The dried ripe seeds of H. pedunculosum ( Herpetospermum caudigerum Wall), with “Se-ji-mei-duo” in Tibet or Chinese name “Bo-Leng-Gua-Zi,” are frequently used for the treatment of “Chiba” diseases caused by liver dysfunction, such as jaundice, hepatitis, cholecystitis [ 1 ]. Modern pharmacological studies have indicated that H. caudigerum contains a variety of bioactive lignans, such as herpetin, herpetfluorenone, and herpetone [ 2 , 3 ], which are mainly responsible for their anti-infammatory [ 1 ], anti-fatigue [ 4 ], anti-hepatitis B virus [ 5 ], anti-cholestatic [ 6 ], and hepatoprotective activities [ 7 – 9 ] ascribed to them. The use of H. pedunculosum in medicine has led to an increasing trend of using this plant as the main ingredient in various medications, such as the “Shi-wei-di-da” capsule, “twenty-five flavors-big soup” pills, and “Jiu-wei-Niu-huang” pills [ 9 ].…”

Section: Introductionmentioning

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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Dehydrodiconiferyl alcohol, a lignan from Herpetospermum pedunculosum, alleviates cholestasis by activating pathways associated with the farnesoid X receptor

Cited by 19 publications

References 32 publications

Natural Products Targeting Liver X Receptors or Farnesoid X Receptor

Natural Products Targeting Liver X Receptors or Farnesoid X Receptor

Glycyrrhetinic Acid Protects α-Naphthylisothiocyanate- Induced Cholestasis Through Regulating Transporters, Inflammation and Apoptosis

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

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