Acute and Subchronic Toxicological Evaluation of the Herbal Product HAD-B1 in Rats

Abstract

This study evaluates acute and subchronic toxicity of a Korean herbal formula HAD-B1 in rat to investigate whether HAD-B1 has potential toxicity to humans. First, the study to assess the acute oral toxicity at dose levels of 0, 500, 1000, and 2000 mg/kg body weight (BW) was performed in male and female SD rats (Crl: CD, specific pathogen-free) (n = 5/group). Based on the result of the acute oral study, 4 weeks’ dose range finding study and 13 weeks’ subchronic study were performed (dose range finding study, DRF; n = 5/group) and 13 weeks (subchronic study; n = 10/group) in male and female SD rats. The control group was administered with distilled water (DW). Clinical signs, body weight, food consumption, ophthalmic examination, urinalysis, hematological/biochemical parameters, gross finding at necropsy, and histopathological examination were investigated and recorded. In the oral acute toxicity study of SD rats, no clinical signs, mortality, body weight changes, and gross findings were observed. Also, there were no treatment-related changes in the 4-week DRF study. Based on these results, a 13-week repeated-dose toxicity study (subchronic) in SD rats was performed. HAD-B1 showed temporal hypersalivation in clinical signs and an increased tendency in body weight at 2000 mg/kg BW. However, there were no treatment-related changes in mortality, food consumption, ophthalmology, urinalysis, hematology, biochemistry, gross finding at necropsy, organ weights, and histopathology in either sex of any group. Based on this toxicological evaluation of HAD-B1, we concluded that no target organ was determined, and the no observed adverse effect level (NOAEL) of HAD-B1 was determined to be > 2000 mg/kg B W. Therefore, we decided that consuming HAD-B1 is relatively nontoxic.

Open-label, single-dosing, the safety and pharmacokinetics of HAD-B1 in healthy male volunteers

“…The previous study demonstrated the safety of HAD-B1 through the toxicological study of long-term and highdosage use (13 weeks, higher than 2000 mg/kg). [8] In vivo and in vitro studies also showed that HAD-B1 has a potential antitumor effect as a growth inhibitor of solid tumors induced by A549 lung cancer cells without remarkable side effects and inhibited the growth of A549 cisplatin-resistant cells in depends on the concentration. [4,5] According to these results, the antitumor effect of HAD-B1 combined with afatinib on H1975 (L858R/T790M double mutation) lung cancer cells was conducted, and the combined treatment of HAD-B1 with afatinib inhibited the proliferation of H1975 cells in a dose-dependent manner without toxicity.…”

“…In an acute and subchronic toxicological evaluation of HAD-B1 in rats, no target organ was determined, and the no observed adverse effect level was >2000 mg/kg BW. [8] In addition, the most effective dosage of HAD-B1 was determined through comparative experiments. Cell experiments (A549, A549/CR) and animal model experiments (lung cancer Xenograft model) determined the most effective composition and dosage.…”

Nonclinical Safety Pharmacology Study of the Herbal Product HAD-B1

“…The test article HAD-B1 used in this study consists of 4 herbs ( Table 1 ). The 3D HPLC analysis of HAD-B1 showed the representative 6 critical compounds including notoginsenoside R1, cordycepin, ginsenoside Rg1, Rb1, α -boswellic acid, and β -boswellic acid [ 20 ]. HAD-B1 was supplied by KyungbangPharm Inc. (Incheon, South Korea).…”

“…Each animal was randomly placed in the test group (T1, T2, T3) and the control group. The dose of HAD-B1 was determined based on the results of the previous 13-week repeated oral administration toxicity test in rats [ 20 ]. No toxicological effects were observed for HAD-B1 up to 2000 mg/kg, thereby determining the no observable adverse effect level (NOAEL) of HAD-B1 to 2000 mg/kg.…”

The Current Status of Integrative Oncology in Korea

“…The prevalence of cancer cases treated with Korean herbal medicine has been widely reported in Korean historical literature. Because of the ease of access to herbal medicine in Korea, taking herbal medicine is a fairly 6 The study on the effects of HAD-B1 on the proliferation of A549 cisplatin-resistant lung cancer cells discovered that the formula inhibited A549CR cell growth in a concentration-dependent manner. 10 Kyunghee University conducted studies on the efficacy and safety of the traditional formula Gamiguibitang with cancer patients who had sleep disturbances, and the results showed that the formula could potentially be used to treat cancer patients' sleep disorders.…”