Throughout history, the issue of population has always been a concern for the stability of human societies, with population expansion or underpopulation ultimately leading to social upheaval or even collapse (Castello, 2012; De Zordo et al., 2022). However, since the Industrial Revolution, human science and technology have progressed rapidly, productivity has risen as never before, and the world's population has grown by leaps and bounds as a result (Parant, 1990). Although the global population is now the largest ever at 7.7 billion and rising, total fertility rates (TFRs) has now almost halved and global TFRs is steadily declining, with 183 of the world's 195 countries and territories projected to have TFRs below replacement level by 2100 (Vollset et al., 2020; Neyer et al., 2022). Banister (1987) proposed that the swift drop in China’s TFRs from 5.8 in 1970 to 2.8 in 1979 was, for the most part, accepted by the Chinese population. This acceptance was presumably due to preceding shifts in the family structure and societal norms (Lavely and Freedman, 1990; Vollset et al., 2020). However, over the last 40 years, China's TFRs has continued to decline, and in 2022, only 9.56 million people will be born in China, 8.15 million fewer than in 2000, resulting in negative endogenous population growth (De Zordo et al., 2022).
Besides the exclusion of uncertainties such as politics, economy, wars, and epidemics, the effects of work pressure, environmental degradation, irregular work and rest, and unhealthy diets have made recurrent miscarriage (RM) one of the main focuses of global TFRs research (Bhattacharya and Bhattacharya, 2009). RM traditionally refers to 3 or more consecutive pregnancy losses within the first 28 weeks of gestation with the same partner. However, current beliefs suggest that patients experiencing 2 consecutive miscarriages face a comparable risk of recurrence to those with 3 consecutive miscarriages (Deng et al., 2022). Reflecting this, the European Society of Human Reproduction and Embryology stipulates that 2 or more miscarriages should be the criterion for RM diagnosis (Stirrat, 1990). Similarly, the American Society for Reproductive Medicine defines RM as 2 or more pregnancy losses occurring before the 20th week of gestation (Deng et al., 2022). RM occurs in 1–2% of all couples attempting to conceive (Bender et al., 2018). Astonishingly, the root causes of almost half of all RM cases remain unidentified, with immune factors implicated in 80% of these unaccounted instances (Li et al., 2021). Acknowledged causes can be traced back to key factors like maternal immunological conditions (including autoimmunity and alloimmune reactions), thrombophilic factors (both genetic predispositions and acquired thrombophilia), anatomical irregularities of the uterus, and endocrine abnormalities (Tise and Byers, 2021). With the complex origin and 50% of unexplained RM, the development of effective treatments and the improvement of live birth rates for RM patients are drawing significant clinical attention (Alijotas-Reig and Garrido-Gimenez, 2013; Ke, 2014).
Prescription for Fertility-preserving Tang (FPT) are formulations developed through the clinical practice of Prof. Liangying Zhang, a nationally renowned practitioner of traditional Chinese medicine (TCM). Prof. Zhang, with nearly five decades of experience in gynecological clinics, teaching, and scientific research, has found these formulations to be highly effective in treating RM (Jiang et al., 2011). FPT is composed of Codonopsis pilosula (Franch.) Nannf. (DangShen, DS), Atractylodes macrocephala Koidz.(BaiZhu, BZ), Angelica sinensis (Oliv.) Diels (DangGui, DG), Rehjnannia glutinosa Libosch. (ShuDiHuang, SDH), Cuscuta chinensis Lam. (TuSiZi, TSZ), Dipsacus asper Wall. ex Henry (XuDuan, XD), Psoralea corylifolia L. (BuGuZhi, BGZ), Ligustrum lucidum Ait. (NüZhenZi, NZZ), Rubus chingii Hu (FuPengZi, FPZ), Litchi chinensis Sonn.(NanShaShen, NSS). Fertility-boosting No. 1 Tang (FB1T) was created by Prof. Jiang Lijuan, Director of the Gynecology Department of Yunnan Provincial Hospital of TCM, the academic successor of Prof. Zhang Liangying, the fourth batch of famous veteran TCM practitioners, according to the characteristics of the clinical use of the FB1T, which is more in line with today's clinical characteristics of RSA, and has a good effect in the treatment of RSA in the clinic. FB1T is composed of DS, BZ, XD), Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao HuangQi, HQ), Eclipta prostrata L. (MoHanLian, MHL), Taxillus chinensi (DC.) Danse (SangJiSheng, SJS), SDH, TSZ, Eucommia ulmoides Oliv. (DuZhong, DZ), Dioscorea opposita Thunb. (Shan Yan, SY), Boehmeria nivea (L.) Gaud. (ZhuMaGen, ZMG), Amomum villosum Lour. (ShaRen, SR), Perilla frutescens (L.) Britt (ZiSuGen, ZSG).
TCM treatments can be tailored according to the patient’s characteristics and changes in the external environment, thus illustrating the principle of individualized prescriptions for the same disease (Sun et al., 2022; Zhang et al., 2019). This principle is best exemplified by FPT and FB1T. Both have shown positive effects on RSA, although their therapeutic material basis and the mechanism of their action remain obscure (Jiang et al., 2011). Previously, we discovered that FB1T can mediate maternal-fetal immune tolerance and prevent the onset of RM by inhibiting the positive feedback loop of the IL-23/Th17 immunoinflammatory axis and regulating the Th17/Treg cell balance (Xingxiu et al., 2022). It is yet to be determined whether FB1T has other mechanisms of action and if FB1T and FPT share the same mechanism of action. Furthermore, multidrug research is a fundamental strategy for the clinical application of TCM. It is widely assumed that the effective components of TCMs are either the chemical constituents of the drugs or their metabolites (He et al., 2022). However, TCMs typically contain thousands of compounds, and these components may vary due to environmental factors or preparation methods. Additionally, the original compounds may undergo comprehensive biological transformations when administered to humans or animals, resulting in a diverse range of metabolites. Therefore, the exhaustive screening of all drug-related compounds from biological matrices poses a substantial challenge.
As molecular biology continues to advance, it opens up exciting new pathways to study the composition and activity of compounds found in herbs (Wang et al., 2021). In this current research endeavor, our objective is to identify the similarities and differences in the active constituents, therapeutic targets, and mechanisms of action of FPT and FB1T in treating RM. Accordingly, we initially identified potential therapeutic active ingredients, targets, and mechanisms of action using network pharmacological analysis. This was followed by virtual validation via molecular docking. Our findings will not only provide theoretical foundations for employing “different formulas for similar patients” in traditional Chinese medicine but also furnish scientific data to support the reproductive clinical application of FB1T and FPT.