Toxicity Assessment of Cadinene Sesquiterpenes from Eupatorium adenophorum in Mice

Ouyang, Canbin; Liu, Xiaoman; Liu, Qi; Bai, Jie; Li, Hou-Yong; Li, Yuan; Wang, Qiuxia; Yan, Dongdong; Mao, Liangang; Cao, Aocheng; Guo, Ming

doi:10.1007/s13659-014-0050-2

Cited by 34 publications

(37 citation statements)

References 45 publications

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“…Pesticides or medicine products must pass a safety evaluation and clinic trials before being approved for public use. In our previous research, we found a significant increase (P<0.01) and decrease (P<0.01) of the spleen index and thymus index with the treatment of DAOA (Ouyang et al 2015). The reduction of the spleen resulted from lowered immune function of the cells, and the severe thymic atrophy resulted from the toxic action of immune system from drugs.…”

Section: Discussionmentioning

confidence: 84%

“…The histopathological images of the spleen and thymus were proof of immunologic function damage. In addition, lymphocyte (LYM) count, red blood cell (RBC) count, and hemoglobin content (HGB) in serum also exhibited significant decreases (P<0.01) on treatment of 300 mg kg −1 BW DAOA and OA (Ouyang et al 2015), which may be mediated by effects associated with the plasma membrane, interference or cellular metabolic pathways. Therefore, any dose that poses a potential risk to the immune system must be larger than 150 mg kg −1 BW of DAOA and OA.…”

Section: -B C 3-b and C)mentioning

confidence: 99%

“…Therefore, toxicity may originate from the cadinene skeleton. From above immune analysis and low toxicity of sesquiterpenes (Ouyang et al 2015), 75 mg kg −1 dose of DAOA/ODA was found to be safe over the span of a 7-day treatment (Wei et al 2011). In light of their low hepato-and immune-toxicity to non-target organisms, such as mice, cadinene sesquiterpenes are a low risk to the environment.…”

Section: -B C 3-b and C)mentioning

confidence: 99%

“…These susquiterpenes are easy to extract and separate. The leaves had low hepatoxicity and good antifungal properties (Jin et al 2014;Liu et al 2015;Ouyang et al 2015). E. adenophorum should be developed for biopesticides or medicinal applications if sesquiterpenes can pass environmental regulations.…”

Section: Introductionmentioning

confidence: 99%

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Immunotoxicity assessment of cadinene sesquiterpenes from Eupatorium adenophorum in mice

Ouyang

Liu

Yan

et al. 2016

Journal of Integrative Agriculture

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Sesquiterpenes in Eupatorium adenophorum are abundant in leaves and have great development potential as biopesticides. The toxicity of sesquiterpenes in immune cells and their corresponding immune functions are not fully understood. We evaluated the immunotoxicity of two cadinene sesquiterpenes 2-deoxo-2-(acetyloxy)-9-oxoageraphorone (DAOA) and 9-oxo-10,11-dehydro-agerophorone (ODA) by using histopathology and toxicology methods in vitro and in vivo in lymphocytes and natural killer cells in Kunming mice. The mice were given single doses of 75, 150 and 300 mg kg −1 body weight (BW) of DAOA/ODA every day for a week. Serious damage to the thymus and spleen was found in tissue images with clear lysis reduction numbers and a loosened arrangement of splenocytes and thymocytes to the mice treated with 150-300 mg kg −1 DAOA/ODA. Mice cytology was also affected with significant cellular alterations, increased splenocytes apoptosis rates (P<0.01), proliferation reduction (P<0.05) and natural killer cells activities reduction (P<0.05) when given 150-300 mg kg −1 DAOA/ODA, the severities of which were dose dependent. However, a 75 mg kg −1 dose of DAOA/ODA showed no change in tissue or cytology after the 7 day treatment, and therefore was considered to be within acceptable safety parameters. Taken together, cadinene sesquiterpenes, as a type of toxic botanical component, have low environmental risks in small doses and should be further studied for their use as biopesticides.

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Section: Discussionmentioning

confidence: 84%

Section: -B C 3-b and C)mentioning

confidence: 99%

Section: -B C 3-b and C)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immunotoxicity assessment of cadinene sesquiterpenes from Eupatorium adenophorum in mice

Ouyang

Liu

Yan

et al. 2016

Journal of Integrative Agriculture

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“…17,18 Euptox A has been found to show hepatotoxicity in rats 19 and immunotoxicity in mice. 6 Therefore, in this study, we aimed to explore the mechanisms underlying the effects of Euptox A on mouse splenocytes. Cell cycle control is a major regulatory mechanism in the process of cell growth, and many cytotoxic substances cause cell death by cell cycle arrest at the G0/ G1, S, or G2/M phases.…”

Section: Discussionmentioning

confidence: 99%

Euptox A Induces G1 Arrest and Autophagy via p38 MAPK- and PI3K/Akt/mTOR-Mediated Pathways in Mouse Splenocytes

Weng

et al. 2017

J Histochem Cytochem.

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Euptox A (9-oxo-10, 11-dehydroageraphorone), the main toxin isolated from Eupatorium adenophorum, is known to induce immunotoxicity in animals. However, the precise mechanism underlying the effects of Euptox A on splenocytes is unclear. Here, we aimed to investigate the molecular mechanisms underlying the effect of Euptox A in mouse spleens after its intragastric administration and found that Euptox A exhibits proautophagic effects in splenocytes. Euptox A markedly arrested the splenocytes in the G0/G1 phase, which was accompanied by inhibition of the expression of the positive regulators CDK4, CDK2, cyclin D1, PCNA, and E2F1, and promotion of the expression of the negative regulators p53, p21 Waf1/Cip1, p27 Kip1, and Chk1. We also found that Euptox A did not markedly induce splenocyte apoptosis, but induced autophagy while increasing the subcellular localization of punctate LC3, ratio of LC3-II/LC3-I, and Beclin 1 levels, and decreasing p62 levels. Euptox A also significantly inhibited p-PI3K, p-p38 MAPK, p-Akt, and p-mTOR expression, but increased PTEN and p-AMPK expression. These results indicated that Euptox A induced splenocyte autophagy by inhibiting the PI3K/Akt/mTOR pathway, suppressing p38 MAPK expression, and activating AMPK. These findings provide new insights into the mechanisms involved in spleen toxicity caused by Euptox A in mice.

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Antifungal Activity of Cadinane‐Type Sesquiterpenes from Eupatorium adenophorum against Wood‐Decaying Fungi

Liu,

Wang,

et al. 2023

Chemistry & Biodiversity

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The present study aimed to evaluate the antifungal activities of Eupatorium adenophorum against four strains of wood‐decaying fungi, including Inonotus hispida, Inonotus obliquus, and Inonotus cuticularis. Bioguided isolation of the methanol extract of E. adenophorum by silica gel column chromatography and high‐performance liquid chromatography afforded six cadinane‐type sesquiterpenes. Their structures were identified by nuclear magnetic resonance and MS analyses. According to the antifungal results, the inhibition rate of the compound was between 59.85 % and 77.98 % at a concentration of 200 μg/mL. The EC50 values ranged from 74.5 to 187.4 μg/mL.

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Toxicity Assessment of Cadinene Sesquiterpenes from Eupatorium adenophorum in Mice

Abstract: Graphical Abstract

Cited by 34 publications

References 45 publications

Immunotoxicity assessment of cadinene sesquiterpenes from Eupatorium adenophorum in mice

Immunotoxicity assessment of cadinene sesquiterpenes from Eupatorium adenophorum in mice

Euptox A Induces G1 Arrest and Autophagy via p38 MAPK- and PI3K/Akt/mTOR-Mediated Pathways in Mouse Splenocytes

Antifungal Activity of Cadinane‐Type Sesquiterpenes from Eupatorium adenophorum against Wood‐Decaying Fungi

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