PI3K/AKT–NF-κB Pathway Modulation By A Kidney‑Tonifying TCM Formula Ameliorates Endometriosis Inflammation in Rats, With Context On Cistanche As A Kidney‑Nourishing Herb

Results

3.1 Comparison of ectopic lesion volumes among groups of rats

No ectopic lesions were observed in the sham-operated group, while ectopic lesions of varying sizes were observed in all other groups. Compared with the model group, the volumes of ectopic lesions were significantly reduced in both the high- and low-dose TCM groups and in the Western medicine group, with statistically significant differences (P<0.01). There was no statistically significant difference among the treatment groups (P>0.05). See Figure 1 and Table 2.

 

Table 2. Volume of Ectopic Lesions in Each Group (x̄ ± s)

Group	n	Volume (mm³)
Sham Operation	10	--
Model	10	274.56 ± 67.36
High-Dose TCM	10	46.28 ± 7.02 **
Low-Dose TCM	10	50.44 ± 3.21 **
Western Medicine	10	45.63 ± 2.14 **

 

 

 

3.2 Morphological observations of uterine and ectopic lesion tissues in each group of rats

H&E staining showed the following: In the sham-operated group, more tall columnar epithelial cells were observed, with a higher number of stromal cells arranged densely and regularly and abundant glands. In the model group, the ectopic lesions contained predominantly cuboidal epithelial cells with small luminal structures; cytoplasm appeared loose and lightly stained, with considerable infiltration of stromal and inflammatory cells and a reduced number of glands. In the high- and low-dose TCM groups and the Western medicine group, larger luminal structures were present, with a small number of degenerated epithelial cells; glandular epithelial cells were atrophic with loose, lightly stained cytoplasm, and there was mild infiltration of inflammatory cells. See Figure 2.

 

3.3 Levels of NF-κB, IL-1β, and IL-6 in serum and peritoneal fluid of each group of rats

ELISA results indicated that, compared with the sham-operated group, the model group had significantly elevated serum NF-κB, IL-1β, and IL-6 levels (P<0.01). Compared with the model group, the high- and low-dose TCM groups and the Western medicine group showed significantly reduced NF-κB, IL-1β, and IL-6 levels in both serum and peritoneal fluid (P<0.05, P<0.01). Between the treatment groups, the high-dose TCM group exhibited lower NF-κB, IL-1β, and IL-6 levels in serum and peritoneal fluid than the low-dose TCM group and the Western medicine group (P<0.05). See Tables 3–4.

 

 

Table 3. Serum Levels of NF-κB, IL-1β, and IL-6 in Each Group of Rats (x̄ ± s)

Group	n	NF-κB (pg/mL)	IL-1β (pg/mL)	IL-6 (pg/mL)
Sham Operation	10	190.88 ± 14.37	15.08 ± 2.56	3.95 ± 0.32
Model	10	302.83 ± 49.47 ##	34.19 ± 0.92 ##	6.90 ± 0.31 ##
High-Dose TCM	10	211.99 ± 19.73 *	20.33 ± 2.16 **	3.21 ± 0.41 **
Low-Dose TCM	10	257.74 ± 21.72 *	27.35 ± 2.99 *	5.03 ± 0.29 *
Western Medicine	10	256.05 ± 22.63 *	24.37 ± 2.14 *	4.97 ± 0.30 *

Note: Compared with sham group: ## P<0.01; Compared with model group: P<0.05, P<0.01.

 

Table 4. Peritoneal Fluid Levels of NF-κB, IL-1β, and IL-6 in Rats (x̄ ± s)

Group	n	NF-κB (pg/mL)	IL-1β (pg/mL)	IL-6 (pg/mL)
Sham Operation	10	60.26 ± 14.13	26.97 ± 2.43	5.42 ± 0.72
Model	10	96.56 ± 9.76 ##	39.66 ± 3.14 ##	8.47 ± 0.87 ##
High-Dose TCM	10	65.93 ± 5.52 **	24.22 ± 3.26 **	5.11 ± 0.43 **
Low-Dose TCM	10	80.94 ± 4.73 **	32.54 ± 1.65 **	6.46 ± 0.33 **
Western Medicine	10	79.37 ± 6.40 **	31.02 ± 0.70 **	6.04 ± 0.33 **

Note: Compared with sham group: ## P<0.01; Compared with model group: P<0.05, P<0.01.

 

CISTANCHE HERB SUPPELEMENTS ON KIDNEY AND PROSTATE HEALTH

Check the listing

 

Supportive Service Of Wecistanche-For more details about cooperation
Email:wallence.suen@wecistanche.com

 

3.4 Immunohistochemical detection of PI3K, AKT, P-AKT, NF-κB, IL-1β, and IL-6 protein expression in uterine and ectopic lesion tissues

Immunohistochemistry showed brown-yellow positive staining for PI3K, AKT, P-AKT, NF-κB, IL-1β, and IL-6, mainly localized in the cytoplasm and nucleus. Compared with the sham-operated group, expression of PI3K, AKT, P-AKT, NF-κB, IL-1β, and IL-6 in uterine tissue was significantly increased in the model group (P<0.01). Relative to the model group, expression of these proteins in uterine tissue was significantly decreased in the high- and low-dose TCM groups and the Western medicine group (P<0.05, P<0.01). Similarly, in ectopic lesion tissues, expression of PI3K, AKT, P-AKT, NF-κB, IL-1β, and IL-6 was significantly decreased in the high- and low-dose TCM groups and the Western medicine group compared with the model group (P<0.05, P<0.01). There were no statistically significant differences among the treatment groups (P>0.05). See Figures 3–4.

3.5 Western blot detection of PI3K, AKT, P-AKT, NF-κB, IL-1β, and IL-6 protein levels in uterine and ectopic lesion tissues
Compared with the sham-operated group, the model group showed significantly increased protein expression of PI3K, AKT, P-AKT, NF-κB, IL-1β, and IL-6 in uterine tissues (P<0.01). Relative to the model group, protein expression levels of PI3K, AKT, P-AKT, NF-κB, IL-1β, and IL-6 in both uterine and ectopic lesion tissues were significantly reduced in the high- and low-dose TCM groups and the Western medicine group (P<0.05, P<0.01). No statistically significant differences were observed among the treatment groups (P>0.05). See Figures 5–6.

3.6 Real-time PCR detection of PI3K, AKT, NF-κB, IL-1β, and IL-6 mRNA levels in uterine and ectopic lesion tissues
Compared with the sham-operated group, the model group showed significantly increased mRNA levels of PI3K, AKT, NF-κB, IL-1β, and IL-6 in uterine tissues (P<0.01). Compared with the model group, the high- and low-dose TCM groups and the Western medicine group had significantly decreased mRNA levels of PI3K, AKT, NF-κB, IL-1β, and IL-6 in both uterine and ectopic lesion tissues (P<0.05, P<0.01). There were no statistically significant differences among the treatment groups (P>0.05). See Tables 5–6.

 

Figure 5. Protein levels of PI3K, AKT, P-AKT, NF-κB, IL-1β, and IL-6 in uterine tissue of rats in each group.

 

Table 5. Uterine mRNA Expression of PI3K, AKT, NF-κB, IL-1β, and IL-6 in Each Group

Group	PI3K	AKT	NF-κB	IL-1β	IL-6
Sham Operation	1.00	1.00	1.00	1.00	1.00
Model	1.81 ± 0.14 ##	1.74 ± 0.10 ##	1.59 ± 0.06 ##	2.77 ± 0.11 ##	1.64 ± 0.17 ##
High-Dose TCM	1.29 ± 0.11 **	1.28 ± 0.09 **	1.04 ± 0.05 **	1.48 ± 0.11 **	1.01 ± 0.05 **
Low-Dose TCM	1.43 ± 0.06 *	1.34 ± 0.10 *	1.20 ± 0.10 **	1.59 ± 0.02 **	1.24 ± 0.10 *
Western Medicine	1.26 ± 0.08 *	1.15 ± 0.05 *	1.02 ± 0.10 *	1.43 ± 0.07 *	1.08 ± 0.08 *

Note: Compared with sham group: ## P<0.01; Compared with model group: P<0.05, P<0.01.

Table 6. Ectopic Lesion mRNA Expression of PI3K, AKT, NF-κB, IL-1β, and IL-6 in Rats

Group	PI3K	AKT	NF-κB	IL-1β	IL-6
Model	1.00	1.00	1.00	1.00	1.00
High-Dose TCM	0.58 ± 0.03 **	0.66 ± 0.02 **	0.47 ± 0.04 **	0.57 ± 0.03 **	0.66 ± 0.03 **
Low-Dose TCM	0.65 ± 0.02 **	0.68 ± 0.04 **	0.51 ± 0.03 **	0.65 ± 0.10 **	0.70 ± 0.03 **
Western Medicine	0.62 ± 0.02 **	0.64 ± 0.03 **	0.46 ± 0.02 **	0.52 ± 0.03 **	0.69 ± 0.02 **

Note: Compared with model group, P<0.01.

 

Discussion

Endometriosis (EMS) is an estrogen-dependent chronic inflammatory disease with an unclear pathogenesis. The most widely accepted mechanism is retrograde menstruation; however, it does not explain why most women experience retrograde flow while only a subset of women of reproductive age develop EMS, nor does it fully explain the diverse locations of ectopic lesions [19]. Current studies suggest that during the development of EMS, biologically active endometrial tissue can enter the peritoneal cavity via retrograde menstruation, disrupt the local immune microenvironment, evade immune surveillance and clearance, and successfully implant outside the uterine cavity [20]. Thus, successful invasion of endometrial cells may be influenced by the extrauterine microenvironment. The presence of abundant macrophages in the peritoneal fluid of EMS patients can release proinflammatory cytokines such as interleukins (ILs) and TNF-α, modulate intercellular communication, promote fibroblast mitosis, and support the implantation of ectopic endometrial tissue [21]. Proinflammatory cytokines can also affect multiple signaling pathways, including NF-κB, IL-6/STAT3, and TGF-β, driving the expression of genes that promote cell survival and proliferation [6,22,23]. Elevated inflammatory mediators in EMS can further upregulate chemokines, enhance the adhesiveness of refluxed endometrial tissues, and create a permissive microenvironment for implantation and angiogenesis [24].

NF-κB is a pivotal regulator of inflammation, and its activation strongly promotes the onset and progression of EMS-related inflammatory responses [25]. Upon activation, the cytoplasmic p50/p65 heterodimer translocates to the nucleus, where it specifically binds to promoter regions of target genes, thereby regulating the expression of multiple inflammatory mediators, including IL-1β, IL-6, and macrophage migration inhibitory factor (MIF), which amplifies EMS-associated inflammation [26,27]. Interleukins are pleiotropic cytokines secreted by macrophages and activated T lymphocytes; they participate in T- and B-cell activation and proliferation during immune responses [28]. IL-1β is a key mediator in inflammatory cascades and can facilitate immune responses and enhance EMS cell invasion via NF-κB signaling [29]. IL-6, a prototypical proinflammatory cytokine, plays essential roles in inflammation, immunity, metabolism, and cancer, modulating immune cell function within the tumor/inflammatory microenvironment and promoting immune evasion [30]. Activated NF-κB in turn induces further release of IL-1β and IL-6, establishing an autocrine/paracrine positive feedback loop that sustains and amplifies local inflammation [31]. In this study, the model rats exhibited elevated NF-κB, IL-1β, and IL-6 in serum and peritoneal fluid, alongside increased protein and mRNA levels of NF-κB, IL-1β, and IL-6 in uterine and ectopic lesion tissues-supporting a scenario of NF-κB activation and heightened proinflammatory cytokine release that fosters an inflammatory microenvironment conducive to ectopic implantation.

The PI3K/AKT pathway is an important upstream regulator of NF-κB. Targeted inhibition of PI3K/AKT signaling has been reported to downregulate IL-1β, NF-κB, and other proinflammatory mediators in rheumatoid arthritis and neuroinflammatory diseases [32–34]. PI3K, a critical intracellular signaling molecule, includes class I/II/III isoforms. Activation can occur through binding to the p110 site of class I PI3K, which then promotes phosphorylation of AKT (e.g., at Ser308), leading to AKT activation [35]. As a key downstream effector, activated AKT can mitigate apoptosis by modulating phosphorylation of proapoptotic proteins and regulating transcription factors. Phosphorylated AKT influences cellular proliferation, differentiation, and migration by regulating downstream effectors such as NF-κB. As a central pathway for maintaining endometrial homeostasis, aberrant activation of PI3K/AKT can increase vascular permeability, remodel extracellular matrix, regulate adhesion/invasion, and promote angiogenesis-collectively supporting the survival and growth of ectopic endometrial tissue and contributing to the pathology of EMS [36]. The activation of PI3K/AKT and NF-κB is crucial for proinflammatory gene expression. The development of EMS is closely associated with immune cell dysfunction, increased immune cell counts, and elevated cytokine levels [25,37]; abnormal inflammatory responses and increased levels of cytokines such as IL-1β and IL-6 have been observed in the endometrium of EMS patients [6,38]. Excessive expression of inflammatory mediators and reduced pelvic clearance of ectopic tissue promote extrauterine growth of ectopic endometrium. In our study, the EMS model group exhibited significantly elevated PI3K, AKT, and phosphorylated AKT in uterine and ectopic lesion tissues. Concomitant activation of the PI3K/AKT pathway aligned with robust expression of NF-κB, IL-1β, and IL-6, intensifying inflammation and disease severity.

 

From the perspective of traditional Chinese medicine (TCM), the essence of EMS is "blood stasis." Guided by the principle of "treating the root," this study used a kidney-tonifying, yang-warming, and blood-stasis-resolving formula for intervention. The formula includes Rougui (Cinnamomi Cortex) and processed Aconite (Aconiti Lateralis Praeparata Radix) to warm kidney yang and support vital fire; Evodia (Evodiae Fructus) and Sangjisheng (Taxilli Herba) to move qi, invigorate blood, and remove pathological products. The prescription aims to address both root and branch: warming kidney yang as the root, and invigorating blood and resolving stasis as the branch, thereby restoring yin–yang balance, correcting pro-/anti-inflammatory imbalance, and regulating aberrant inflammatory responses. Prior research has shown that this formula alleviates EMS-related clinical symptoms with definite efficacy and few adverse reactions [12]. Modern pharmacology suggests anti-inflammatory actions of its constituents: cinnamaldehyde in Rougui can inhibit excessive cytokine release and modulate immunity and gut microbiota to relieve inflammation [39]; Aconite combined with Atractylodes macrocephala appears to modulate inflammatory pathways, immune networks, and proteolytic metabolism [40]; Sangjisheng aqueous extracts suppress inflammatory responses and proliferation of inflammatory cells [41]; evodiamine (EVO), an indoloquinazoline alkaloid from Evodia, can attenuate inflammation by inhibiting TLR4/IRAK1/NF-κB signaling [42,43]. Our experimental results show that the kidney-tonifying, yang-warming, and blood-stasis-resolving formula significantly downregulated transcription and protein expression of PI3K, AKT, NF-κB, and downstream inflammatory cytokines IL-1β and IL-6 in uterine and ectopic lesions of EMS model rats. Serum and peritoneal fluid levels of NF-κB, IL-1β, and IL-6 were also markedly reduced, suggesting that the formula may ameliorate the local lesion microenvironment by suppressing PI3K/AKT activation and NF-κB nuclear translocation, thereby decreasing proinflammatory cytokine secretion to achieve therapeutic benefit in EMS.

Note on Cistanche (added context for readers, consistent with TCM theory and literature):
Within TCM, Cistanche (Cistanche deserticola; "Rou Cong Rong") is a classic kidney-tonifying herb often discussed in the context of nourishing kidney yang and supporting reproductive health. While Cistanche was not a component tested in the above animal experiment, pharmacological studies and traditional usage suggest potential immunomodulatory and anti-inflammatory properties aligned with the therapeutic rationale of kidney-tonifying formulas. For readers seeking background on Cistanche's kidney-nourishing role, see: Cistanche for nourishing kidney (TCM herb for prevent you from kidney disease), product and science overview: https://www.xjcistanche.com/cistanche-extract-product/cistanche-for-nourishing-kidney.html. This external resource provides source information and scientific references that may help contextualize how kidney-tonifying herbs are positioned in TCM. Any incorporation of Cistanche into EMS-related regimens should be based on targeted preclinical/clinical studies and practitioner guidance.

 

Limitations

This is an animal study, and mechanistic exploration remains limited. Future work can integrate cell-based experiments to deepen mechanistic insights. Given the multi-component, multi-target, and multi-pathway characteristics of TCM formulas, subsequent studies may leverage network pharmacology, transcriptomics, and proteomics to further elucidate pharmacodynamics and mechanisms, thereby providing a theoretical basis for the clinical application of the kidney-tonifying, yang-warming, and blood-stasis-resolving formula in EMS.

 

Conflict of interest
None declared.

 

 

References

[1] Agostinis C, Balduit A, Mangogna A, et al. Immunological Basis of Endometriosis: The Complement System as a Potential Therapeutic Target. Front Immunol. 2021;11:599117.
[2] Wang Y, Nicholes K, Shih IM. The Origin and Pathogenesis of Endometriosis. Annu Rev Pathol. 2020;15:71–95.
[3] Vallvé-Juanico J, Houshdaran S, Giudice LC. The endometrial immune environment of women with endometriosis. Hum Reprod Update. 2019;25(5):564–591.
[4] Zou G, Wang J, Xu X, et al. Cell subtypes and immune dysfunction in peritoneal fluid of endometriosis revealed by single-cell RNA-sequencing. Cell Biosci. 2021;11(1):98.
[5] Wei Y, Liang Y, Lin H, et al. Autonomic nervous system and inflammation interaction in endometriosis-associated pain. J Neuroinflammation. 2020;17(1):80.
[6] Zhou WJ, Yang HL, Shao J, et al. Anti-inflammatory cytokines in endometriosis. Cell Mol Life Sci. 2019;76(11):2111–2132.
[7] Scott J, Rees L, Gallimore A, Lauder SN. PI3K Isoform Immunotherapy for Solid Tumours. Curr Top Microbiol Immunol. 2022;436:369–392.
[8] Madanes D, Bilotas MA, Bastón JI, et al. PI3K/AKT pathway is altered in the endometriosis patient's endometrium and presents differences according to severity stage. Gynecol Endocrinol. 2020;36(5):436–440.
[9] Liu Y, Qin X, Lu X, et al. Effects of inhibiting the PI3K/Akt/mTOR signaling pathway on the pain of sciatic endometriosis in a rat model. Can J Physiol Pharmacol. 2019;97(10):963–970.
[10] Zhong S, Liu L. Analysis of the correlation between TLR4 pathway and aberrant proliferation and invasion in endometriosis lesions. Chin J Matern Child Health Care. 2019;34(14):3345–3348. (in Chinese)
[11] Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244–1256.
[12] Yang J, Li QX, Tong RX, et al. Effects of warming kidney and resolving stasis on serum BK and PGF2α in patients with kidney-deficiency and blood-stasis type endometriosis. Shizhen Traditional Chinese Medicine and Materia Medica. 2020;31(05):1152–1154. (in Chinese)
[13] Meng X, Fu X, An M, et al. Mechanistic study of Bushen Wenyang Huayu Decoction regulating SIRT1–FoxO1-mediated autophagy to treat endometriosis. China J Chin Mater Med. 2024;39(05):2542–2548. (in Chinese)
[14] Li Y, Meng X, Fu X, et al. Bushen Wenyang Huayu Decoction targets TLR4/NF-κB–mediated autophagy to treat endometriosis effectively. Evid Based Complement Alternat Med. 2022;2022:426341.
[15] Zhang Y, Cao H, Zhang CJ. Establishment of an improved rat model of endometriosis and observation of microvessel density. Chin J Lab Anim Sci. 2008;(01):56–58,79. (in Chinese)
[16] Jia Y, Du H, Yao YY. Establishment and evaluation of a rat model of endometriosis with kidney-yang deficiency and blood stasis. Hebei J TCM. 2017;32(03):9–12,18. (in Chinese)
[17] Dai B, Zhang JN, Yang ML, et al. Establishment of a hydrocortisone-induced kidney-deficiency mouse model and related index evaluation. Chin J Lab Anim Sci. 2017;25(01):70–73. (in Chinese)
[18] Lu JJ, Dai XY, Li X, et al. Effects of sulforaphane on eutopic endometrial proliferation, angiogenesis, and JAK2/STAT3 signaling in a rat model of endometriosis. Chin J Immunol. 2021;37(11):1297–1301,1307. (in Chinese)
[19] Casalechi M, Di Stefano G, Fornelli G, et al. Impact of endometriosis on the ovarian follicles. Best Pract Res Clin Obstet Gynaecol. 2024;92:102430.
[20] Sampson CS, White K. Endometriosis: An Unusual Cause of Bilateral Pneumothoraces. Clin Pract Cases Emerg Med. 2020;4(1):35–37.
[21] Wang Y, Dragovic RA, Greaves E, Becker CM, Southcombe JH. Macrophages and small extracellular vesicle–mediated intracellular communication in the peritoneal microenvironment: Impact on endometriosis development. Front Reprod Health. 2023;5:1130849.
[22] Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018;18(5):309–324.
[23] Sikora J, Smycz-Kubańska M, Mielczarek-Palacz A, et al. The involvement of multifunctional TGF-β and related cytokines in the pathogenesis of endometriosis. Immunol Lett. 2018;201:31–37.
[24] Donnez J, Cacciottola L. Endometriosis: An inflammatory disease that requires new therapeutic options. Int J Mol Sci. 2022;23(3):1518.
[25] Hoesel B, Schmid JA. The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer. 2013;12:86.
[26] Reis FM, Petraglia F, Taylor RN. Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update. 2013;19(4):406–418.
[27] Morotti M, Vincent K, Brawn J, Zondervan KT, Becker CM. Peripheral changes in endometriosis-associated pain. Hum Reprod Update. 2014;20(5):717–736.
[28] Yang Q, Zhang LF. Interleukin family cytokines and stem cell mobilization. Chin J Comp Med. 2011;21(5):62–65. (in Chinese)
[29] Li N, Chen L, Feng XL. NF-κB signaling and the pathogenesis of endometriosis: research and targeted therapy. Chin J Immunol. 2019;35:509–514. (in Chinese)
[30] Kishimoto T, Kang S. IL-6 revisited: From rheumatoid arthritis to CAR T cell therapy and COVID-19. Annu Rev Immunol. 2022;40:323–348.
[31] Wang S, Zhang W, Song DR. Roles of NF-κB in the pathogenesis of endometriosis. Int J Obstet Gynecol. 2022;49(4):461–465. (in Chinese)
[32] Gong Y, Qiu J, Jiang T, et al. Maltol ameliorates intervertebral disc degeneration by inhibiting PI3K/AKT/NF-κB and regulating NLRP3 inflammasome-mediated pyroptosis. Inflammopharmacology. 2023;31(1):369–384.
[33] Wang Y, Lin Y, Wang L, et al. TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling in Alzheimer's disease mice. Aging (Albany NY). 2020;12(20):20862–20879.
[34] Shi X, Jie L, Wu P, et al. Calycosin mitigates chondrocyte inflammation and apoptosis by inhibiting PI3K/AKT and NF-κB pathways. J Ethnopharmacol. 2022;297:115536.
[35] Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;296(5573):1655–1657.
[36] Qin R, Zheng F, Qin W, et al. Progranulin promotes proliferation, migration and invasion via PI3K/AKT signalling in a model of endometriosis. Reprod Biomed Online. 2023;46(3):425–435.
[37] Bai C, Yang X, Zou K, et al. Anti-proliferative effect of RCE-4 from Reineckia carnea on HeLa cells by inhibiting PI3K/Akt/mTOR and NF-κB activation. Naunyn Schmiedebergs Arch Pharmacol. 2016;389(6):573–584.
[38] Vetvicka V, Laganà AS, Salmeri FM, et al. Regulation of apoptotic pathways during endometriosis: from the molecular basis to the future perspectives. Arch Gynecol Obstet. 2016;294(5):897–904.
[39] Yang HL, Wu X. Advances in mechanisms of cinnamaldehyde and cinnamon extracts in colorectal inflammation and cancer prevention. Shandong Med. 2025;65(01):119–122,128. (in Chinese)
[40] Tan JS, Huang FQ, Zhao X. Network pharmacology and molecular docking analysis of Aconite–Atractylodes macrocephala for knee osteoarthritis. TCM Rehabilitation. 2025;2(03):47–55. (in Chinese)
[41] Yi CX, Hong ZS, Tan LP, et al. Preliminary experimental study on the anti-inflammatory effects of Taxilli Herba. Pharm Res. 2019;38(02):70–72,94. (in Chinese)
[42] Li X, Ge J, Zheng Q, et al. Evodiamine and rutaecarpine from Tetradium ruticarpum in the treatment of liver diseases. Phytomedicine. 2020;68:153180.
[43] Zeng FG, Wang KZ, Fan LY, et al. Effects of evodiamine on LPS-induced osteoblast inflammation via TLR4/IRAK1/NF-κB axis. Chin J Gerontol. 2025;45(01):195–199. (in Chinese)

SEO note for discoverability (kept concise): TCM herb for prevent you from kidney disease; Cistanche (Rou Cong Rong) as a kidney-tonifying herb; PI3K/AKT and NF-κB in endometriosis; anti-inflammatory cytokines IL-1β, IL-6; traditional Chinese medicine intervention in EMS.