Experimental study of the anti-tumour activity and pharmacokinetics of arctigenin and its valine ester derivative

Cai, Enbo; Song, Xingzhuo; Han, Mei; Yang, Limin; Zhao, Yan; Li, Wei; Han, Jiahong; Tu, Shumei

doi:10.1038/s41598-018-21722-1

Cited by 11 publications

(9 citation statements)

References 43 publications

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“…After intravenous injection of arctigenin, the plasma concentration–time data in piglets conformed to the non-absorbed two-compartment model. These results were similar to those of a previous study, which evaluated intravenous injection of different doses of arctigenin and its valine ester derivative in Wistar rats (21). The blood drug concentration–time curve was consistent with the two-compartment model.…”

Section: Discussionsupporting

confidence: 91%

“…After oral administration of Fructus arctii, the blood concentration–time data of arctigenin in piglets were consistent with the two-compartment model of absorption. This is not in line with the characteristics of the one-compartment model after Wistar rats were orally administered different doses of arctiin and its valine ester derivative, which was reported by Cai et al (21). These differences may have been species specific.…”

Section: Discussioncontrasting

confidence: 56%

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Pharmacokinetics of Arctigenin and Fructus Arctii Powder in Piglets

Zhang²,

Yang

et al. 2019

Front. Vet. Sci.

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Fructus arctii, also known as great power seed, is the dried fruit of Arctium lappa of the family Compositae. It is a commonly used veterinary herbal medicine, and arctigenin is the main active ingredient. The aim of this study was to characterize the absorption, distribution, metabolism, and excretion of arctigenin and Fructus arctii powder in piglets. These data were used to provide a theoretical reference for the development and clinical use of new veterinary drugs. Sixteen healthy piglets (mean weight 30.0 ± 5.0 kg) were divided into two groups. One group was administered 2.0 mg/kg body weight (bw) arctigenin intravenously, and the other was administered 1.0 g/kg . bw Fructus arctii powder by gavage. Blood samples were collected from the anterior vena cava at different time points, and the concentration of arctigenin in the plasma of the piglets was determined using high-performance liquid chromatography (HPLC). Arctigenin conformed to a two-compartment model with no absorption, and the main pharmacokinetic parameters were as follows: distribution half-life ( t 1/2α )−0.166 ± 0.022 h; elimination half-life ( t 1/2β )−3.161 ± 0.296 h; apparent volume of distribution ( V d )−0.231 ± 0.033 L/kg; clearance rate (CL b )−0.057 ± 0.003 L/(h.kg); and area under the curve (AUC)−1.189 ± 0.057 g . h/mL. The pharmacokinetic parameters of arctigenin following oral administration of the Fructus arctii powder were as follows: absorption half-life ( t 1/2ka )−0.274 ± 0.102 h, t 1/2α −1.435 ± 0.725 h, t 1/2β −63.467 ± 29.115 h, V d −1.680 ± 0.402 L/kg, CL b −0.076 ± 0.028 L/(h kg), peak time ( t max )−0.853 ± 0.211 h, peak concentration ( C max )−0.430 ± 0.035 g/mL, and AUC−14.672 ± 4.813 g/mL. These results indicated that intravenous arctigenin was sparingly distributed in tissues. In contrast, orally administered Fructus arctii powder was rapidly absorbed, more widely distributed, and more slowly eliminated than the intravenous arctigenin, which may indicate its sustained pharmacological effects.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 56%

Pharmacokinetics of Arctigenin and Fructus Arctii Powder in Piglets

Zhang²,

Yang

et al. 2019

Front. Vet. Sci.

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“…As we know, the potential toxicities of Arctigenin were reported previously. Repeated subcutaneous injection of large doses of Arctigenin can induce injury to the liver and biliary duct in Beagle dogs (Cai et al, 2018 ). Meanwhile, 7-day continuous oral exposure demonstrated that Arctigenin (9 mg/kg/day) evidently aggravated apoptosis in the kidney tissue, especially in tubular cells in kidney I/R mice, which implied that Arctigenin had potential renal injury effect (Han et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

28-Day Oral Chronic Toxicity Study of Arctigenin in Rats

et al. 2018

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Arctium lappa (burdock) is the most popular daily edible vegetable in China and Japan because of its general health tonic effects. Previous studies focused on the beneficial role of Arctigenin but neglected its potential side-effects and toxicities. In the present study, the sub-chronic toxicity profile of Arctigenin following 28 days of consecutive exposure was investigated in rats. The results showed that during the drug exposure period, Arctigenin-12 mg/kg administration resulted in focal necrosis and lymphocytes infiltration of heart ventricular septal muscle cells. In the kidney cortical zone, the renal tubular epithelial cells were swollen, mineralized, and lymphocyte infiltrated. In the liver, the partial hepatocyte cytoplasm showed vacuolation and fatty changes, focal necrosis, and interstitial lymphocyte infiltration. In the rats that underwent 36 mg/kg/day administration, there was bilateral testis and epididymis atrophy. In the lung and primary bronchus, erythrocytes and edema fluid were observed. Changes of proestrus or estrus were observed in the uterus, cervix, and vagina intimal epithelial cells. Lymphocytic focal infiltration occurred in the prostate mesenchyme. The high dosage of Arctigenin only decreased the body weight at day 4. At the end of the recovery period, histopathological changes were irreversible, even after withdrawal of the drug for 28 days. Focal necrosis still existed in the heart ventricular septal muscle cells and hepatocytes. Lymphocyte infiltrations were observed in the heart, renal cortex, hepatocyte, and pancreas exocrine gland. Meanwhile, atrophy occurred in the testicles and pancreas. In addition, in the Arctigenin-12 mg/kg group, creatinine (CREA) and brain weight were both significantly increased. The toxicokinetical study demonstrated that Arctigenin accumulated in the organs of rats. The food consumption, hematological, and biochemical parameters were not associated with the above results. These contradictory results might result from the lesions induced by Arctigenin, which were not sufficiently serious to change the parameters. These results suggest that Arctium lappa should be consumed daily with caution because of the potential toxicity induced by Arctigenin. According to all results, the lowest observed adverse effect level (LOAEL) was induced by 12 mg/kg daily exposure to Arctigenin, and the No-observed-adverse-effect-level (NOAEL) should be lower than 12 mg/kg.

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“…Several studies have established that there are three morphological categories of liver tumors in dogs [14][15][16][17]: (1) Massive tumors within a single lobe of the liver -this is the most well-verified category; (2) nodular or multifocal formations involving several lobes [18][19][20]; and (3) diffuse tumors occurring across the entire area of the liver [21][22][23][24]. If researchers gain more precise information about how the structural variability of liver tumors in dogs affects life expectancy, clinicians will be better able to make differential diagnoses of various liver pathologies and conduct necessary treatment on time [25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Influence of hepatic neoplasia on life expectancy in dogs

et al. 2020

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Background and Aim: The present study investigated the influence of liver tumor structure on life expectancy in dogs. Diseases of the liver comprise 5-25% of all non-communicable diseases in dogs, and primary hepatic tumors account for 0.6-1.3% of tumors. This research aimed to study the post-operative life span of animals with primary or metastatic tumors of the liver. Materials and Methods: During the study period, 7124 oncological operations were performed in our clinic. In total, 128 liver tumors were detected in live animals, while 323 were detected posthumously. Forty animals underwent surgery for various liver tumors. In dogs with primary liver tumors, the average age was 11.9 years and the average body weight was 15.5 kg, while in dogs with liver metastases, the mean age was 11.4 years and the average body weight was 24 kg. Results: The ratio of males to females among dogs with primary liver tumors was about 1:1 (ten females and nine males), while that among dogs with metastatic liver damage was clearly predominantly female (14 females and two males) because females often undergo surgery for cancerous mammary glands or ovaries. Conclusion: The size of tumors and the number of affected lobes had a significant effect on the post-operative life span. With a tumor size of <5 cm and a lesion covering less than two lobes of the liver, life expectancy was significantly longer and the prognosis was more favorable. In cases of large tumors or those affecting more than two lobes, life expectancy was significantly reduced and the prognosis was cautious to unfavorable.

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Experimental study of the anti-tumour activity and pharmacokinetics of arctigenin and its valine ester derivative

Cited by 11 publications

References 43 publications

Pharmacokinetics of Arctigenin and Fructus Arctii Powder in Piglets

Pharmacokinetics of Arctigenin and Fructus Arctii Powder in Piglets

28-Day Oral Chronic Toxicity Study of Arctigenin in Rats

Influence of hepatic neoplasia on life expectancy in dogs

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