Studying the nature of ascending-descending-floating-sinking of Chinese medicines based on gonadotropin-releasing hormone

doi:10.19852/j.cnki.jtcm.20220516.003

Abstract

Abstract:

OBJECTIVE: to explore the nature of ascending-descending-floating-sinking of Traditional Chinese Medicine on normal rats using gonadotropin-releasing hormone (GnRh). METHODS: Normal male Sprague-Dawley rats were orally administered six floating Chinese medicines and seven sinking Chinese medicines for 14 d. then, GnRh and relevant indicators were detected. Initially, the different effects of floating and sinking drugs on the body were explored. To verify the effects of floating and sinking drugs on the body, normal rats were orally administered Mahuang (Herba Ephedra Sinica) and Tinglizi (Semen Lepidii Apetali) for 14 d. Then, GnRh antagonists were administered. We observed the changes of relevant indicators and clarified the correlation between GnRh and the laws of floating and sinking. RESULTS: Floating Chinese medicines significantly increased the testicular coefficients; GnRh level in the serum; the protein level of GnRh receptor (GnRhR) in the testis; and the mRNA levels of androgen receptor (AR), small C-terminal domain phosphatase (SCP) 3, SCP2, SYCE1, SMC1B, SMC3, and Rec8 (P < 0.01 or < 0.05). Sinking Chinese medicines did not react similarly, while GnRh antagonists blocked the regulatory effect of Mahuang (Herba Ephedra Sinica) but did not affect Tinglizi (Semen Lepidii Apetali). CONCLUSIONS: GnRh may be closely related to the nature of ascending-descending-floating-sinking of Chinese medicine. Floating Chinese medicines may promote their medicinal properties by regulating GnRH level; however, sinking Chinese medicines did not affect GnRh level.

Key words: gonadotropin-releasing hormone, receptors, LHRH, Mahuang (Herba Ephedra Sinica), Tinglizi (Semen Lepidii Apetali), testis, ascending-descending-floating-sinking.

FU Yang, YUAN Peipei, ZENG Mengnan, HOU Ying, GAO Liyuan, WEI Yaxin, ZHENG Xiaoke, FENG Weisheng. Studying the nature of ascending-descending-floating-sinking of Chinese medicines based on gonadotropin-releasing hormone[J]. Journal of Traditional Chinese Medicine, 2022, 42(4): 546-555.

Figures/Tables 10

Table 1 Primer sequences

Target	Forward Primer (5’-3’)	Reverse Primer (5’-3’)
GnRhR	GGCATTTGCCACCTCCTTTG	ATAAGTGGGTCGAAGCACGG
AR	ATCAAGCTGGAGAACCCGTC	CTAGCCAAGTCCCCATAGCG
SCP3	CGGAGCAGCTGAACAAACATC	TGGTGGTTTCCCAGATTTCCC
SYCP2	TGATGCAAGTGGATCACAGATTC	CTGCTGCTGTTGTCTGGTTC
REC8	ACGTGGTAAAGACCTGCGAG	AAGCTGGGCGGAGAGATAGA
SYCE1	GGGGTACAGATCCTTGCTCA	CGCTCTTGGACTGTCTCCTT
SMC1B	GTAGATGCAGCCCTGGACAA	GGGTAGACGCCTATCAGTGC
SMC3	GCACTTGCCGCTAAGAGAGA	TCCGCCGGAAATGGTCTAAC
GAPDH	ACAGCAACAGGGTGGTGGAC	TTTGAGGGTGCAGCGAACTT

Table 2 Main chemicals in typical floating and sinking Chinese medicines

Chinese medicine	Main chemical
Mahuang (Herba Ephedra Sinica)	Ephedrine, Pseudoephedrine ²
Chaihu (Radix Bupleuri Chinensis)	Saikosaponin a, Saikosaponind ³
Shengma (Rhizoma Cimicifugae Foetidae)	Cimigenol, Cimicifugoside, 25-Omethylcimicgenol, Dahurinol, Dehydroxydahurinol ⁴
Gegen (Radix Puerariae Lobatae)	Puerarin, 3-hydroxy Puerarin, Kudzusapogenol C&A ⁵
Bohe (Herba Menthae Haplocalycis)	L-Menthol, Menthone, L-Menthone, Menthyl acetate N-decyl Acetate ⁶
Jiegeng (Radix Platycodi)	Platycodigenin, PlatycodinD⁷
Dingxiang (Flos Syzygii Aromatici)	Eugenol, Isoeugenol, Eugenyl acetate ⁸
Kuxingren (Semen Armeniacae Amarum)	Amygdalin ⁹
Chuanniuxi (Radix Cyathulae)	Cyasterone ¹⁰
Fuling (Poria)	Dehydrotumulosic acid, Polyporenic acid C, DehydropachyMic acid, Pachymic acid¹¹
Daodou (Canavaliae Semen)	Gallic acid, β-sitosterol, Lupeol ¹²
Xuanfuhua (Flos Inulae Japonicae)	Inulicin, Inunolide, Chlorogenic acid¹³
Tinglizi (Semen Lepidii Apetali)	Quercetin 3-O-β-D-glucose-7-O-β-D-gentiobioside, Sinapin tyiocyante ¹⁴
Chuanxiong (Rhizoma Chuanxiong)	Ligustilide, Senkyunolide A, Senkyunolide I ¹⁵

Figure 1 Effects of typical floating and sinking Chinese treatments on testicular coefficient and sex hormone levels in normal male rats A: testis index of each group of rats; B-D: levels of GnRH, LH, and testosterone (T) of each group of rats. NC: Normal control group; MH: Mahuang (Herba Ephedra Sinica); CH: Chaihu (Radix Bupleuri Chinensis); SM: Shengma (Rhizoma Cimicifugae Foetidae); GG: Gegen (Radix Puerariae Lobatae); BH: Bohe (Herba Menthae Haplocalycis); JG: Jiegeng (Radix Platycodi); DX: Dingxiang (Flos Syzygii Aromatici); KXR: Kuxingren (Semen Armeniacae Amarum); CNX: Chuanniuxi (Radix Cyathulae); FL: Fuling (Poria); DD: Daodou (Canavaliae Semen); XFH: Xuanfuhua (Flos Inulae Japonicae); TLZ: Tinglizi (Semen Lepidii Apetali); CX: Chuanxiong (Rhizoma Chuanxiong). GnRh: gonadotropin-releasing hormone; LH: luteinising hormone; T: testosterone. MH (4.2 g/kg), CH (7 g/kg), SM (7 g/kg), GG (10.5 g/kg), BH (4.2 g/kg), JG (7 g/kg), DX (2.1 g/kg), KXR (7 g/kg), CNX (7 g/kg), FL (10.5 g/kg), DD (6.3 g/kg), XFH (6.3 g/kg), TLZ (7 g/kg), and CX (7 g/kg) were administered to the rats of different groups by oral gavage. The data represent the mean ± standard deviation of eight rats in each group. Compared with the normal group, aP < 0.01, bP < 0.05.

Figure 2 Effect of typical floating and sinking Chinese medicines on GnRhR expression in the testis of normal male rats A: effect of typical floating Chinese medicines on GnRhR expression in the testis of normal male rats; B: effect of typical sinking Chinese medicines on GnRhR expression in the testis of normal male rats.NC: Normal control group; MH: Mahuang (Herba Ephedra Sinica); CH: Chaihu (Radix Bupleuri Chinensis); SM: Shengma (Rhizoma Cimicifugae Foetidae); GG: Gegen (Radix Puerariae Lobatae); BH: Bohe (Herba Menthae Haplocalycis); JG: Jiegeng (Radix Platycodi); DX: Dingxiang (Flos Syzygii Aromatici); KXR: Kuxingren (Semen Armeniacae Amarum); CNX: Chuanniuxi (Radix Cyathulae); FL: Fuling (Poria); DD: Daodou (Canavaliae Semen); XFH: Xuanfuhua (Flos Inulae Japonicae); TLZ: Tinglizi (Semen Lepidii Apetali); CX: Chuanxiong (Rhizoma Chuanxiong). MH (4.2 g/kg), CH (7 g/kg), SM (7 g/kg), GG (10.5 g/kg), BH (4.2 g/kg), JG (7 g/kg), DX (2.1 g/kg), KXR (7 g/kg), CNX (7 g/kg), FL (10.5 g/kg), DD (6.3 g/kg), XFH (6.3 g/kg), TLZ (7 g/kg), and CX (7 g/kg) were administered to the rats of different groups by oral gavage. GnRhR: gonadotropin-releasing hormone receptor. The data represent the mean ± standard deviation of eight rats in each group. The data represent the mean ± standard deviation of eight rats in each group. Compared with the normal group, aP < 0.05, bP < 0.01.

Table 3 Effects of typical floating Chinese medicines on sperm meiosis-related mRNA levels in the testis of normal male rats ($\bar{x}±s$)

Group	n	GnRhR	AR	SCP3	SYCE1	SMC1B	SMC3	SYCP2	REC8
MH	8	2.44±0.67^a	1.75±0.33^b	1.29±0.10^a	1.31±0.18^b	1.40±0.06^a	1.46±0.24^b	2.78±0.37^a	1.64±0.22^a
CH	8	2.63±0.47^a	1.72±0.45^b	1.24±0.16^a	1.31±0.13^b	1.38±0.23^b	1.43±0.21^b	1.66±0.33	1.44±0.02^b
SM	8	2.00±0.19^a	2.10±0.68^a	1.42±0.03^a	1.36±0.10^b	1.40±0.08^a	2.04±0.10^a	1.99±0.75^b	1.41±0.03^b
GG	8	1.50±0.14^b	2.04±0.64^a	1.33±0.06^a	1.35±0.08^b	1.57±0.29^a	1.41±0.14^b	2.80±0.67^a	1.83±0.15^a
BH	8	1.44±0.03	1.66±0.65	1.19±0.19	1.26±0.25	1.27±0.08	1.14±0.08	1.18±0.26	1.28±0.12
JG	8	1.69±0.35^a	1.95±0.75^a	1.4±0.03^a	1.28±0.14^b	1.65±0.25^a	1.84±0.12^a	2.77±1.04^a	2.13±0.19^a
NC	8	1.00±0.32	1.00±0.17	1.00±0.22	1.00±0.02	1.00±0.03	1.00±0.26	1.00±0.44	1.00±0.24

Table 4 Effects of typical sinking Chinese medicines on sperm meiosis-related mRNA levels in the testis of normal male rats ($\bar{x}±s$)

Group	n	GnRhR	AR	SCP3	SYCE1	SMC1B	SMC3	SYCP2	REC8
DX	8	0.82±0.3	0.57±0.01	0.59±0.16^b	0.51±0.02^b	0.64±0.05^b	0.90±0.23	0.96±0.46	0.39±0.17^b
KXR	8	0.44±0.16^a	0.58±0.03	0.59±0.16^b	0.63±0.11^b	0.89±0.14	1.36±0.16	0.66±0.19	0.37±0.10^b
CNX	8	0.75±0.34	1.46±0.77	0.60±0.02^b	0.50±0.06^b	0.78±0.14^b	1.02±0.17	0.69±0.13	0.69±0.04^a
FL	8	0.88±0.04	1.01±0.43	0.59±0.09^b	0.49±0.08^b	0.64±0.04^b	1.09±0.22	0.96±0.38	0.58±0.25^a
DD	8	0.75±0.01	0.99±0.36	0.62±0.08^b	0.44±0.03^b	0.60±0.12^b	0.83±0.07	1.33±0.25	0.57±0.01^a
XFH	8	0.50±0.12^a	1.17±0.51	0.57±0.05^b	0.57±0.05^b	0.67±0.02^b	1.00±0.28	0.80±0.28	0.71±0.01
TLZ	8	0.82±0.04	1.63±0.93	0.50±0.05^b	0.46±0.08^b	0.58±0.02^b	1.11±0.22	1.17±0.49	0.54±0.06^b
NC	8	1.00±0.32	1.00±0.33	1.00±0.22	1.00±0.31	1.00±0.03	1.00±0.11	1.00±0.21	1.00±0.13

Figure 3 Effects of MH and TLZ with cetrorelix on testicular coefficient and sex hormone levels in normal male rats A: testis index of each group of rats; B-D: levels of GnRH, LH, and testosterone (T) of each group of rats. MH (4.2 g/kg) and TLZ (4.2 g/kg) were administered by oral gavage for the different groups. Each antagonist group injected intraperitoneally 300 µg·kg-1·d-1 cetrorelix. The data represent the mean ± standard deviation of eight rats in each group. NC: Normal control group; NC+CE: Normal + cetrorelix group; MH: Mahuang (Herba Ephedra Sinica) group; MH+CE: Mahuang (Herba Ephedra Sinica) + cetrorelix group; TLZ: Tinglizi (Semen Lepidii Apetali) group; TLZ+CE: Tinglizi (Semen Lepidii Apetali) + cetrorelix group. The data represent the mean ± standard deviation of eight rats in each group. Compared with the normal group, aP < 0.05, bP < 0.01; compared with the MH group; cP < 0.01.

Figure 4 Effects of MH and TLZ with cetrorelix on protein levels of GnRhR, AR, and SCP3 in the testis of normal male rats using immunofluorescence assay A, B: effects of MH and TLZ with cetrorelix on protein levels of GnRhR, AR, and SCP3 in the testis of normal male rats. MH (4.2 g/kg) and TLZ (4.2 g/kg) were administered by oral gavage for the different groups. Each antagonist group injected intraperitoneally 300 µg·kg-1·d-1 cetrorelix. NC: Normal control group; NC + CE: Normal + cetrorelix group; NC: Normal control group; NC + CE: Normal + cetrorelix group; MH: Mahuang (Herba Ephedra Sinica) group; MH + CE: Mahuang (Herba Ephedra Sinica) + cetrorelix group; TLZ: Tinglizi (Semen Lepidii Apetali) group; TLZ + CE: Tinglizi (Semen Lepidii Apetali) + cetrorelix group. GnRhR: gonadotropin-releasing hormone receptor; AR: androgen receptor; SCP3: Synaptonemal complex protein 3. The data represent the mean ± standard deviation of eight rats in each group. Compared with the normal group, aP < 0.01, bP < 0.05; compared with the MH group; cP < 0.01.

Figure 5 Effects of MH and TLZ with cetrorelix on protein levels of GnRhR, AR, and SCP3 in the testis of normal male rats using Western blotting MH (4.2 g/kg) and TLZ (4.2 g/kg) were administered by oral gavage for the different groups. Each antagonist group injected intraperitoneally 300 µg·kg-1·d-1 cetrorelix. NC: Normal control group; NC+CE: Normal + cetrorelix group; NC: Normal control group; NC+CE: Normal + cetrorelix group; MH: Mahuang (Herba Ephedra Sinica) group; MH+CE: Mahuang (Herba Ephedra Sinica) + cetrorelix group; TLZ: Tinglizi (Semen Lepidii Apetali) group; TLZ+CE: Tinglizi (Semen Lepidii Apetali) + cetrorelix group. GnRhR: gonadotropin-releasing hormone receptor. The data represent the mean ± standard deviation of eight rats in each group. Compared with the normal group, aP < 0.05.

Table 5 Effects of MH and TLZ with cetrorelix on sperm meiosis-related mRNA levels in the testis of normal male rats ($\bar{x}±s$)

Group	n	GnRhR	AR	SCP3	SYCE1	SMC1B	SMC3	SYCP2	REC8
NC	8	1.00±0.30	1.00±0.04	1.00±0.07	1.00±0.05	1.00±0.07	1.00±0.05	1.00±0.23	1.00±0.30
NC+CE	8	0.44±0.15^a	0.60±0.14^a	0.52±0.22^b	0.78±0.02	0.62±0.09^a	0.68±0.05^b	0.29±0.05^b	0.38±0.07^a
MH	8	1.41±0.18^b	1.29±0.02^b	1.58±0.26^a	1.63±0.59^a	1.59±0.18^a	1.37±0.24^b	1.58±0.37^a	1.73±0.12^b
MH+CE	8	0.82±0.11^c	0.70±0.12^c	1.04±0.09^d	0.57±0.30^c	1.20±0.10^c	0.65±0.23^c	0.58±0.19^c	0.71±0.34^c
TLZ	8	1.04±0.07	0.91±0.12	1.02±0.29	0.74±0.06	0.61±0.01	0.99±0.11	0.89±0.26	0.51±0.28
TLZ+CE	8	0.16±0.10^a	0.59±0.07^a	0.46±0.21^b	0.62±0.17	0.31±0.02^a	0.68±0.07^b	0.39±0.15^b	0.13±0.10^a

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