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Study on the potential nephrotoxicity and mutagenicity of aristolochic acid IVa and its mechanism.

Previous reports demonstrated that aristolochic acids (AAs) exposure-induced nephrotoxicity, mutations, and tumorigenesis are mainly due to aristolochic acid I (AAI). Notably, the chemical structure of aristolochic acid IVa (AAIVa), which exists at higher levels in many Aristolochiaceae herbs, is extremely similar to AAI. In lack of toxicological data, it is unknown whether AAIVa exposure leads to aristolochic acid nephropathy (AAN), mutations, and tumorigenesis as of AAI. To answer these questions, mice were administered AAIVa by single or repeated long-term gavage, while AAI was used as a po…

[Textual Research on Chiding Disease and Matixiang Herb in Da he wai ke (External Medicine of Da He)].

Recorded in Da he wai ke (The External Medicine of Da He) in the Ming dynasty without a corresponding disease title in contemporary scholarl … iang is probably deduced as Asarum forbesii Maxim., A. ichangense C. Y. Cheng et C. S. Yang, family Aristolochiaceae, or Valeriana jatamansi Jones., family Valerianaceae.

The effect of isoquinoline alkaloids on opiate withdrawal.

Our interest has been centered on isoquinoline alkaloids obtained from Argemone mexicana (Papaveraceae), Aristolochia constricta (Aristolochiaceae) and the opium alkaloid, papaverine. In this respect, the effect of these isoquinoline alkaloids was investigated on contractions induced by naloxone of isolated guinea pig ileum acutely exposed to morphine in vitro. The activity of these alkaloids was compared to the control compound, papaverine. Furthermore, the effect of these isoquinoline alkaloids was also determined on naloxone-precipitated withdrawal in isolated guinea pig ileum exposed to DA…

Activation of LONP1 by 84-B10 alleviates aristolochic acid nephropathy via re-establishing mitochondrial and peroxisomal homeostasis.

Pharmaceutical formulations derived from Aristolochiaceae herbs, which contain aristolochic acids (AAs), are widely used for medicinal purposes. However, exposure to these plants and isolated AAs is linked to renal toxicity, known as AA nephropathy (AAN). Currently, the mechanisms underlying AAN are not fully understood, leading to unsatisfactory treatment strategies. In this study, we explored the protective role of 84-B10 (5-[[2-(4-methoxyphenoxy)-5-(trifluoromethyl) phenyl] amino]-5-oxo-3-phenylpentanoic acid) against AAN. RNA-seq analysis revealed that the mitochondrion and peroxisome were…

Urotensin II enhances transforming growth factor‑β1 expression and secretion in the kidney during aristolochic acid nephropathy.

Aristolochic acid is a component of many types of Chinese medicine, which are commonly used to treat almost all human diseases. However, aristolochic acid may cause nephropathy. Urotensin II (UII) and transforming growth factor (TGF)‑β1 are important signaling factors, which are expressed at elevated levels during the development of nephropathy. However, the association between UII and TGF‑β1 expression remains unclear. In the current study, the regulatory association between UII and TGF‑β1 expression was investigated using a rat aristolochic acid nephropathy model and the NRK‑52E cell line. T

NANOS3-YTHDF2 drives aberrant P-body accumulation to impair folliculogenesis in offspring of maternal aristolochic acid I exposure.

Processing-bodies (PBs) are cytoplasmic membraneless condensates essential for RNA regulation. They share structural and functional similarities with germ granules and are critical for primordial folliculogenesis, a developmental process highly susceptible to exogenous insults. Aristolochic acid I (AAⅠ), a pervasive environmental toxin from Aristolochiaceae plants, is known to cross the placental barrier and induce fetal ovarian oxidative stress. Here, using a mouse model of maternal AAⅠ exposure (16.5 to 18.5 days post-coitus), we demonstrate that this prenatal insult causes profound defects …

[Textual research on Wumei Pills].

Wumei Pills originates from Treatise on Cold Damage. A total of 128 records on it were screened out, involving 102 ancient books, 110 modern … e medicinal selection, Zanthoxyli Pericarpium is examinable. Asari Radix et Rhizoma is derived from Aristolochiaceae, which is toxic to the liver and kidney, so the dosage should be kept in a safe range. In summary, Wumei Pills has great clinical value. The textual research on Wumei Pills helps clarify the development of Wumei Pills, which provides evidence in-dep …

Role of immune dysregulation in aristolochic acid-induced multisystem toxicities: an insight from systems toxicology.

Exposure to aristolochic acids [AAs, including aristolochic acid Ⅰ (AAⅠ), aristolochic acid Ⅱ (AAⅡ), and aristololactam Ⅰ (ALⅠ)] has cast a shadow over public health due to the global therapeutic usage of the Aristolochiaceae herbs comprising AAs. Evidence is mounting that AAs exposure is definitely responsible for multisystem toxicities. The toxicological landscape of AAs, implicating toxic effects, toxicity targets, and toxicity signaling pathways, has yet to be thoroughly disentangled. We used the structure information of AAⅠ, AAⅡ, and ALⅠ to outline AAs multisystem toxicities. AAs targets …

Phytochemical Screening by HRLC-MS/MS (Q-TOF) and Antioxidant and Anti-Inflammatory Properties of Thottea sivarajanii Leaf Extract.

Background: Numerous degenerative diseases are brought on by inflammation and oxidative stress. Metabolites from plants contain anti-inflammatory and antioxidant properties. Indigenous and understudied, Thottea sivarajanii is a significant ethnobotanical herb. It is native to the Western Ghats and belongs to the Aristolochiaceae family. Objectives: The current study investigated the antioxidant and anti-inflammatory properties of T. sivarajanii leaf methanol extract (TSL) and the insights provided by phytochemical analysis. Methods: The HRLC-MS/MS (Q-TOF) study is used for the phytochemical an…

Traditional uses, phytochemistry, pharmacology, and toxicology of Akebiae Caulis and its synonyms: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: "Mutong" ( in Chinese, and generally known as Akebiae Caulis), which refers to a group of herbal medicines w … , and other properties of Akebiae Caulis. Among the species used, Aristolochiae manshuriensis Kom. (Aristolochiaceae) contains aristolochic acid that has raised concerns globally because of its nephrotoxicity. CONCLUSIONS: Clarifying the biological origin of traditional herbal medicines is critical for their safe and effective use. The present review revealed tha …

Comparison of Aristolochic acid I derived DNA adduct levels in human renal toxicity models.

Aristolochic acid (AA) dependent human nephropathy results either from environmental exposure to Aristolochiaceae plant subspecies or their use in traditional phytotherapy. The toxic components are structurally related nitrophenanthrene carboxylic acids, i.e. Aristolochic acid I (AAI) and II (AAII). AAI is considered to be the major cause of Aristolochic acid nephropathy, characterized by severe renal fibrosis and upper urothelial cancer. Following enzymatic activation in kidney and/or liver, AAI metabolites react with genomic DNA to form persistent DNA adducts with purines. To determine wheth…

Evaluation of the nephrotoxicity and safety of low-dose aristolochic acid, extending to the use of Xixin (Asurum), by determination of methylglyoxal and d-lactate.

ETHNOPHARMACOLOGICAL RELEVANCE: Most Aristolochiaceae plants are prohibited due to aristolochic acid nephropathy (AAN), except Xixin (Asarum spp.). Xixin contains trace amounts of aristolochic acid (AA) and is widely used in Traditional Chinese Medicine. Methylglyoxal and d-lactate are regarded as biomarkers for nephrotoxicity. AIM OF THE STUDY: The use of Xixin (Asarum spp.) is essential and controversial. This study aimed to evaluate tubulointerstitial injury and interstitial renal fibrosis by determining urinary methylglyoxal and d-lactate after withdrawal of low-dose AA in a chronic mouse…

Deceptive Aristolochia Trap-Flowers Pollinated by Male Phorid Flies Mimic Volatiles Specific to Female Phorids.

BACKGROUND AND AIMS: Floral mimicry is a form of deceptive pollination in which flowers or inflorescences imitate specific resources relevant to potential flower visitors, such as food, brood sites, or mating partners (sexual mimicry). A plant genus containing many unstudied species with potentially highly diverse deceptive systems is fly-pollinated Aristolochia (Aristolochiaceae), famous for its trap flowers. A few species with strongly male-biased pollinator assemblages have been suggested to mimic the female sex pheromones of flies. However, so far, neither the floral scents nor the female …

Untargeted DNA Adductomics Identifies Aristolochic Acid III as a Potent DNA-Damaging Agent among 11 Substituted Aromatic Genotoxicants in the Rat Urinary System.

An untargeted, data-independent acquisition high-resolution accurate tandem mass spectrometry method using an Orbitrap mass spectrometer was … itrophenanthro[3,4-d]-1,3-dioxole-5-carboxylic acid (AA-I), a naturally occurring genotoxicant from Aristolochiaceae plants, were the most abundant across most organs, forming both 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) adducts. In contrast, significantly lower DNA adduct levels were formed with the aromatic amine 4-aminobiphenyl and 2-nitrofluorene, an …

Comparative volatile profiling of Asarum species and MaxEnt-based habitat assessment of Asarum sieboldii: implications for species authentication, geographical origin traceability, and climate-informed conservation.

INTRODUCTION: Asarum sieboldii Miq. (Aristolochiaceae) is an important medicinal plant characterized by substantial chemotypic variation. However, the potential of this variation for species authentication and geographical origin traceability, together with the effects of future climate change on its suitable habitats, remains insufficiently understood. METHODS: We conducted two complementary analyses to evaluate the chemical differentiation and habitat suitability of A. sieboldii. Seventy two wild individuals from 12 populations, comprising seven populations of A. sieboldii and one populatio…

Chemotaxonomy of the ethnic antidote Aristolochia indica for aristolochic acid content: Implications of anti-phospholipase activity and genotoxicity study.

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochia indica L. (Aristolochiaceae) is a common medicinal plant described in many traditional medicine as well as in Ayurveda used against snakebites. Besides, the plant has also been reported traditionally against fever, rheumatic arthritis, madness, liver ailments, dyspepsia, oedema, leishmaniasis, leprosy, dysmenorrhoea, sexual diseases etc. The plant is known to contain its major bioactive constituent aristolochic acid (AA) known for its anti-snake venom, abortifacient, antimicrobial and antioxidant properties. MATERIALS AND METHODS: This present work…

An imprecise probability approach-based determination of over-represented southern African plant genera and families used in ethnopharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The analyses of patterns of over-representation of southern African traditional medicinal plants at the genu … and Dicoma, Combretaceae and Pterocelastrus, Ebenaceae and Bersama, Francoaceae and Erythrina, and Aristolochiaceae and Strychnos for plants used in the treatment of STIs, febrile and mosquito-vector diseases, microbial infections, pain, skin conditions, and female sexual/reproductive problems, respectively. CONCLUSIONS: Genus-level calculations are more efficie …

Human UDP-glucuronosyltransferase 1As catalyze aristolochic acid D O-glucuronidation to form a lesser nephrotoxic glucuronide.

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochic acids (AAs) are naturally occurring nitro phenanthrene carboxylic acids primarily found in plants of the Aristolochiaceae family. Aristolochic acid D (AAD) is a major constituent in the roots and rhizomes of the Chinese herb Xixin (the roots and rhizomes of Asarum heterotropoides F. Schmidt), which is a key material for preparing a suite of marketed Chinese medicines. Structurally, AAD is nearly identical to the nephrotoxic aristolochic acid I (AAI), with an additional phenolic group at the C-6 site. Although the nephrotoxicity and metabolic pathway…

Modulation of Lonp1 Activity by Small Compounds.

The Lon protease homolog 1 (LONP1) is an ATP-dependent mitochondrial protease essential for maintaining proteostasis, bioenergetics, and cellular homeostasis. LONP1 plays a pivotal role in protein quality control, mitochondrial DNA maintenance, and oxidative phosphorylation system (OXPHOS) regulation, particularly under stress conditions. Dysregulation of LONP1 has been implicated in various pathologies, including cancer, metabolic disorders, and reproductive diseases, positioning it as a promising pharmacological target. This review examines compounds that modulate LONP1 activity, categorizin

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… This role of 84-B10 as an activator of LONP1 has been further confirmed in another study, where it was tested against aristolochic acid nephropathy (AAN), a form of renal toxicity linked to Aristolochiaceae -derived aristolochic acids (AAs). …

The versatile emodin: A natural easily acquired anthraquinone possesses promising anticancer properties against a variety of cancers.

Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and

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… also reported in plants in several other families, such as Aloe vera ( Asphodelaceae ), Acorus tatarinowii ( Araceae ), Cassia obtusifolia ( Leguminosae ), Cassia occidentalis ( Leguminosae ), Eriocaulon buergerianum ( Eriocaulaceae ), Dendrobium thyrsiflorum ( Orchidaceae ), Fibraurea tinctoria ( Aristolochiaceae …