Anti-inflammatory, anti-tussive effects and toxicity evaluation of Qingfei Dayuan granules (清肺达原颗粒)

doi:10.19852/j.cnki.jtcm.20230404.003

Abstract

Abstract:

OBJECTIVE: To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules (清肺达原颗粒, QFDY), and to evaluate the acute and sub-chronic toxicity of QFDY.
METHODS: Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice. Ear swelling degree was calculated and tumor necrosis factor-α, interleukin-1β and interleukin-6 were determined. Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor. Latent period cough and number of cough within 3 min were counted. In acute toxicity study, the rats were randomly divided into test group and solvent control group. Body weighs, food intakes and general clinical signs were monitored. In the sub-chronic toxicity study, QFDY was administered to rats at 0, 4, 8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted. Mortalities, clinical signs, body weight changes, food intakes, ophthalmological examinations, hematological parameters, biochemical indicators, electrolyte indicators, urinalyses and histopathological examinations were monitored.
RESULTS: QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor. The results presented a dose-effect relationship. In acute toxicity study, no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period. In the sub-chronic toxicity study, higher reticulocyte count, lymphocyte and lower Cl-, blood urea nitrogen were analyzed compared with the solvent control group. But the differences were considered to be incidental and not clinically toxic. Obvious dose-effect relationship of urine color was observed, and the three test groups at the end of the experiments resulted in significant increase in urobilinogen, bilirubin, ketone body and urine leukocyte. However, all the positive indicators returned to normal in the recovery period. Therefore, no toxicological changes were found during the study period.
CONCLUSION: QFDY showed significant anti-inflammatory and anti-tussive effects in mice. The lethal dose (LD50) of per oral QFDY in rats was estimated to be more than 24.0 g/kg per day and the no observed adverse effect level was over 16 g/kg per day, which suggested that QFDY is relatively safe for oral medication at the present dose on rats. Our experimental results provide a reference for the further development and research of QFDY.

Key words: anti-inflammatory agents, anti-tussive, toxicity tests, acute, sub-chronic toxicity, Qingfei Dayuan granules

CHENG Huanbo, HU Hui, SUN Daihua, WANG Guangzhong. Anti-inflammatory, anti-tussive effects and toxicity evaluation of Qingfei Dayuan granules (清肺达原颗粒)[J]. Journal of Traditional Chinese Medicine, 2023, 43(6): 1110-1117.

Figures/Tables 6

Figure 1 Effects of QFDY on swelling degree and inflammatory cytokines in the xylene-induced ear edema in mice model A: swelling degree; B: TNF-α; C: IL-1β; D: IL-6. SC groups: treated with distilled water; AC groups: treated with 520 mg/kg aspirin; LQ, MQ, and HQ groups were given 3.90, 5.46 and 7.80 g/kg QFDY per day, respectively, each group was administered once a day for 7 d. SC: solvent control group; AC: aspirin control group; LQ: low-dose group; MQ: medium-dose group; HQ: high-dose groups; TNF-α: tumor necrosis factor-α; IL-1β: interleukin-1β; IL-6: interleukin-6. aP < 0.01, bP < 0.05, significantly different compared with SC group; cP < 0.05, significantly different compared with AC group.

Table 1 Effects of QFDY on the ammonia liquor induced cough in mice ($\bar{x}$ ± s)

Group	n	Dose	Latent period cough (s)	No. of coughs	Inhibition (%)	Cough Activity (%)
SC	10	0 g/kg	7.6±1.3	41.2±12.7	-	-
PC	10	25 mg/kg	16.5±6.8^a	12.0±3.6^b	70.9	-
LQ	10	3.90 g/kg	12.4±4.9	39.1±12.4	5.1	7.2
MQ	10	5.46 g/kg	13.1±2.8^b	25.4±6.3^a	38.3	54.1
HQ	10	7.80 g/kg	18.9±3.7^b	14.1±3.5^b	65.8	92.8

Figure 2 Effects of sub-chronic toxicity experiment of QFDY on mean body weight and food intake A: body weight in male; B: body weight in female; C: food intake in male; D: food intake in female. SC groups: treated with distilled water; LQ, MQ, and HQ groups were given 4, 8 and 16 g/kg QFDY per day, respectively, each group (n = 30, 15 males and 15 females) was administered once a day for 28 and 30 d of post treatment was conducted. SC: solvent control group, LQ: low-dose group, MQ: medium-dose group, HQ: high-dose groups. aP < 0.05, bP < 0.001, significantly different compared to the SC group.

Table 2 Effects of QFDY on urine indexes in end of treatment period (rat numbers)

Parameter	Level	Males					Females
Parameter	Level	SC	LQ	MQ	HQ		SC	LQ	MQ	HQ
UBG	-	10	10	10	7	10		9	10	6
	±	0	0	0	0	0		0	0	0
	+	0	0	0	3	0		1	0	4^a
BIL	-	10	10	8	2	10		8	9	3
	±	0	0	0	0	0		0	0	0
	+	0	0	2	8^b	0		2	1	7^b
KET	-	5	0	0	0	10		8	7	2
	±	5	9	7	4	0		2	3	8^b
	+	0	1^a	3^a	6^b	0		0	0	0
LEU	-	0	0	0	0	0		0	1	0
	±	1	1	0	0	4		0	1	0
	+	8	9	9	5	6		9	7	5
	++	1	0	1	4	0		1	1	5^c
	+++	0	0	0	1^a	0		0	0	0

Table 3 Effects of QFDY granules on urine indexes in end of recovery period (rat numbers)

Parameter	Level	Males					Females
Parameter	Level	SC	LQ	MQ	HQ		SC	LQ	MQ	HQ
UBG	-	5	5	5	5	5		5	5	5
	±	0	0	0	0	0		0	0	0
	+	0	0	0	0	0		0	0	0
BIL	-	4	5	4	5	5		5	5	5
	±	0	0	0	0	0		0	0	0
	+	1	0	1	0	0		0	0	0
KET	-	3	2	0	0	5		5	5	5
	±	1	3	4	4	0		0	0	0
	+	1	0	1	1	0		0	0	0
LEU	-	0	0	0	0	1		0	0	0
	±	0	2	1	0	2		3	2	5
	+	5	3	4	5	1		2	3	0
	++	0	0	0	0	1		0	0	0
	+++	0	0	0	0	0		0	0	0

Figure 3 Histological findings of SC group and HQ group in the recovery period A: histological findings of SC group in lungs (10 × 40); B: histological findings of HQ group in lungs (10 × 40); C: histological findings of SC group in livers (10 × 20); D: histological findings of HQ group in livers (10 × 20); E: histological findings of SC group in kidneys (10 × 20); F: histological findings of HQ group in kidneys (10 × 10). SC groups: treated with distilled water, HQ groups: given 16 g/kg QFDY per day, each group (n = 30) was administered once a day for 28 and 30 d of post treatment was conducted. All stained with hematoxylin-eosin. SC: solvent control group; HQ: high-dose groups.

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