Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome

Wang, Feixuan; Zhu, Nan; Zhou, Fan; Lin, Dong-Xiang

doi:10.3390/molecules26206117

Cited by 26 publications

(12 citation statements)

References 105 publications

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“…The presence of many aporphine alkaloids is remarkable, notably in the oxazoloaporphine series (e.g., artabonatine). These products could be useful to combat various metabolic diseases, such as type 2 diabetes mellitus, endothelial dysfunction, hypertension and cardiovascular diseases [ 128 ]. There are also interesting flavones (artabotrysides A-B) and lactones (artapetalins A-C), not found or rarely in other plants, which would deserve further studies.…”

Section: Discussionmentioning

confidence: 99%

Advocacy for the Medicinal Plant Artabotrys hexapetalus (Yingzhao) and Antimalarial Yingzhaosu Endoperoxides

Bailly

Hénichart

2022

Molecules

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The medicinal plant Artabotrys hexapetalus (synonyms: A. uncinatus and A. odoratissimus) is known as yingzhao in Chinese. Extracts of the plant have long been used in Asian folk medicine to treat various symptoms and diseases, including fevers, microbial infections, ulcers, hepatic disorders and other health problems. In particular, extracts from the roots and fruits of the plant are used for treating malaria. Numerous bioactive natural products have been isolated from the plant, mainly aporphine (artabonatines, artacinatine) and benzylisoquinoline (hexapetalines) alkaloids, terpenoids (artaboterpenoids), flavonoids (artabotrysides), butanolides (uncinine, artapetalins) and a small series of endoperoxides known as yingzhaosu A-to-D. These natural products confer antioxidant, anti-inflammatory and antiproliferative properties to the plant extracts. The lead compound yingzhaosu A displays marked activities against the malaria parasites Plasmodium falciparum and P. berghei. Total syntheses have been developed to access yingzhaosu compounds and analogues, such as the potent compound C14-epi-yingzhaosu A and simpler molecules with a dioxane unit. The mechanism of action of yingzhaosu A points to an iron(II)-induced degradation leading to the formation of two alkylating species, an unsaturated ketone and a cyclohexyl radical, which can then react with vital parasitic proteins. A bioreductive activation of yingzhaosu A endoperoxide can also occur with the heme iron complex. The mechanism of action of yingzhaosu endoperoxides is discussed, to promote further chemical and pharmacological studies of these neglected, but highly interesting bioactive compounds. Yingzhaosu A/C represent useful templates for designing novel antimalarial drugs.

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Section: Discussionmentioning

confidence: 99%

Advocacy for the Medicinal Plant Artabotrys hexapetalus (Yingzhao) and Antimalarial Yingzhaosu Endoperoxides

Bailly

Hénichart

2022

Molecules

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“…The aporphine alkaloids have been isolated from a variety of plants, including the genera Glaucium flavum, Beilschmiedia elliptica, and Nandina domestica. They are known to be promising agents in the prevention and treatment of metabolic syndrome due to their broad biological activity, including antihypertension, antidiabetes, antiobesity, antioxidation, and anti-inflammation . In particular, many of the aporphines show various levels of preventing insulin resistance and regulation of glucose homeostasis.…”

Section: Benzyltetrahydroisoquinoline Alkaloidsmentioning

confidence: 99%

“…In particular, many of the aporphines show various levels of preventing insulin resistance and regulation of glucose homeostasis. The methoxy and hydroxyl substituents may be important for these biological activities …”

Section: Benzyltetrahydroisoquinoline Alkaloidsmentioning

confidence: 99%

Recent Advances in the Total Synthesis of the Tetrahydroisoquinoline Alkaloids (2002–2020)

Kim

Ngamnithiporn

et al. 2023

Chem. Rev.

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The tetrahydroisoquinoline (THIQ) natural products constitute one of the largest families of alkaloids and exhibit a wide range of structural diversity and biological activity. Ranging from simple THIQ natural products to complex trisTHIQ alkaloids such as the ecteinascidins, the chemical syntheses of these alkaloids and their analogs have been thoroughly investigated due to their intricate structural features and functionalities, as well as their high therapeutic potential. This review describes the general structure and biosynthesis of each family of THIQ alkaloids as well as recent advancements of the total synthesis of these natural products from 2002 to 2020. Recent chemical syntheses that have emerged harnessing novel, creative synthetic design, and modern chemical methodology will be highlighted. This review will hopefully serve as a guide for the unique strategies and tools used in the total synthesis of THIQ alkaloids, as well as address the longstanding challenges in their chemical and biosynthesis.

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“…To the organs’ protection effect, Nuci exerts excellent pharmacological therapy in disease models of kidney, liver, bone, and nervous system [ 3 ]. In the research area of liver injury, most reports focus on the Nuci-mediated metabolism regulation through glutathione (GSH), superoxide dismutase, inflammatory cytokines, and bile acid, so the liver metabolic disease models such as non-alcoholic fatty liver disease and hepatocellular steatosis are widely applied for investigation [ 4 ]. However, the liver metabolic disease of rodents needs a long time to construct models, which belong to non-acute exposure.…”

Section: Introductionmentioning

confidence: 99%

Nuciferine Effectively Protects Mice against Acetaminophen-Induced Liver Injury

Zhou

et al. 2023

Antioxidants

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Acetaminophen (APAP) overdose still poses a major clinical challenge and is a leading cause of acute liver injury (ALI). N-acetylcysteine (NAC) is the only approved antidote to treat APAP toxicity while NAC therapy can trigger side effects including severe vomiting and even shock. Thus, new insights in developing novel therapeutic drugs may pave the way for better treatment of APAP poisoning. Previous research has reported that nuciferine (Nuci) possesses anti-inflammatory and antioxidant properties. Therefore, the objective of this study was proposed to investigate the hepatoprotective effects of Nuci and explore its underlying mechanisms. Mice were intraperitoneally (i.p.) administered with APAP (300 mg/kg) and subsequently injected with Nuci (25, 50, and 100 mg/kg, i.p.) at 30 min after APAP overdose. Then, all mice were sacrificed at 12 h after APAP challenge for further analysis. Nuci-treated mice did not show any side effects and our results revealed that treating Nuci significantly attenuated APAP-induced ALI, as confirmed by histopathological examinations, biochemical analysis, and diminished hepatic oxidative stress and inflammation. The in silico prediction and mRNA-sequencing analysis were performed to explore the underlying mechanisms of Nuci. GO and KEGG enrichment of the predicted target proteins of Nuci includes reactive oxygen species, drug metabolism of cytochrome P450 (CYP450) enzymes, and autophagy. Furthermore, the mRNA-sequencing analyses indicated that Nuci can regulate glutathione metabolic processes and anti-inflammatory responses. Consistently, we found that Nuci increased the hepatic glutathione restoration but decreased APAP protein adducts in damaged livers. Western blot analysis further confirmed that Nuci effectively promoted hepatic autophagy in APAP-treated mice. However, Nuci could not affect the expression levels of the main CYP450 enzymes (CYP1A2, CYP2E1, and CYP3A11). These results demonstrated that Nuci may be a potential therapeutic drug for APAP-induced ALI via amelioration of the inflammatory response and oxidative stress, regulation of APAP metabolism, and activation of autophagy.

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Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome

Cited by 26 publications

References 105 publications

Advocacy for the Medicinal Plant Artabotrys hexapetalus (Yingzhao) and Antimalarial Yingzhaosu Endoperoxides

Advocacy for the Medicinal Plant Artabotrys hexapetalus (Yingzhao) and Antimalarial Yingzhaosu Endoperoxides

Recent Advances in the Total Synthesis of the Tetrahydroisoquinoline Alkaloids (2002–2020)

Nuciferine Effectively Protects Mice against Acetaminophen-Induced Liver Injury

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