Multi-Target Pharmacological Actions Of Cistanche Deserticola: From Kidney Protection To Immune Modulation
Jun 26, 2025
2. Pharmacological Activities of Cistanche deserticola
2.1 Anti-Tumor Effects
Cancer remains one of the leading causes of mortality worldwide [50]. As molecular oncology advances, targeted therapies that act on specific signaling pathways have become a research hotspot. Interestingly, multi-target natural compounds from Traditional Chinese Medicine (TCM), such as those found in Cistanche deserticola, have shown promising roles in:
Inhibiting tumor cell proliferation
Sensitizing cancer cells to chemotherapy
Reversing drug resistance [51–53]
Recent studies have identified several bioactive compounds from Cistanche with anti-cancer activity through multiple signaling pathways.
40% Echinacoside Cistanche Extract
2.1.1 Hepatocellular Carcinoma (HCC)
Echinacoside was shown by Ye et al. [54] to inhibit HepG2 liver cancer cell proliferation by downregulating TREM2 and suppressing PI3K/Akt phosphorylation, inducing apoptosis.
Total glycosides of Cistanche deserticola (TG) demonstrated dual inhibitory mechanisms [55–56]:
Wnt/β-catenin pathway suppression: Activates GSK-3β, promotes β-catenin degradation, and arrests the cell cycle.
Mitochondrial apoptosis activation: Upregulates Bax, activates Caspase-3, and promotes HepG2 cell death.
Tubuloside B, another active compound, inhibited Hippo-YAP signaling, increasing YAP-Ser127 phosphorylation and suppressing downstream oncogenes like CTGF, CYR61, and N-cadherin, thereby reducing HCC cell migration and invasion [57].
2.1.2 Colorectal Cancer and Drug Resistance Modulation
Jia et al. [58] found that Cistanche extract reduced Helicobacter infection, enhanced macrophage activity, and upregulated NOS II, suppressing colorectal mucosal hyperplasia.
Xu Wei et al. [8] showed that Cistanche aqueous extract downregulated MRP1 and p53, triggering autophagy and apoptosis in MG-63 osteosarcoma cells, thus improving methotrexate sensitivity.
2.1.3 Tumor-Related Complications: Cancer-Related Fatigue (CRF)
Zhang et al. [59] revealed that Cistanche extract modulates the HIF-1α/BNIP3L/Beclin-1 pathway, enhancing HIF-1α and BNIP3L while inhibiting excessive autophagy. This improved oxidative stress and muscle atrophy, offering a novel target for CRF treatment.
🧬 Cistanche's anti-tumor effects are mediated via multiple signaling cascades: Hippo-YAP, Wnt/β-catenin, HIF-1α/BNIP3L/Beclin-1, and mitochondrial apoptotic pathways (see Fig. 1).
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2.2 Neuroprotective and Cognitive-Enhancing Effects
Cistanche deserticola is rich in phenylethanoid glycosides (PHGs), such as echinacoside and acteoside, which demonstrate multi-pathway neuroprotection:
Ischemic stroke
Neurodegenerative diseases
Neuropathic pain
Cognitive decline and depression
2.2.1 Protection Against Ischemic Brain Injury
Liu et al. [61] showed that PHGs activated the Wnt/β-catenin pathway, stimulating neural stem cell (NSC) proliferation and improving recovery in a middle cerebral artery occlusion (MCAO) mouse model [62].
Xu Xia et al. [63] confirmed that acteoside enhances Wnt/β-catenin signaling, increases Bax and Caspase-3, and attenuates hypoxia-induced apoptosis and inflammation in neonatal rats.
2.2.2 Neuroinflammation and Pain Modulation
Liu et al. [64] found that echinacoside targets the P2X7R/FKN/CX3CR1 axis, inhibits p38 MAPK phosphorylation, and reduces microglial inflammation, alleviating neuropathic pain [65].
2.2.3 Ferroptosis Inhibition & Cognitive Improvement
Zhang et al. [66] demonstrated that PHGs inhibit neural ferroptosis via two mechanisms:
Upregulating ACSL4 and LPCAT3 to reduce lipid peroxidation
Enhancing GPX4 to maintain redox homeostasis and improve cognition under hypoxia [67–68]
Ye et al. [69] reported that combining TG (total glycosides) with Lycium barbarum polysaccharides increased GSH-Px activity, improved neurotransmitter metabolism (via ChAT), and mitigated age-related memory decline.
2.2.4 Depression and Hormonal Regulation
Wang et al. [72] found that Cistanche decoction inhibits MAO, reduces dopamine degradation, and alleviates oxidative stress, offering a novel antidepressant mechanism.
Cistanche polysaccharides (CDPs) exhibited androgen-like effects by downregulating TGF-α and HIF-1α, showing potential as natural hormone replacement therapy [73–75].
2.2.5 Neurodegenerative Diseases: Alzheimer's & Parkinson's
Alzheimer's Disease (AD):
Zhou et al. [76] verified that echinacoside reduced Aβ deposition, tau hyperphosphorylation, and improved synaptic plasticity.
Miao Xin et al. [77] showed that acteoside activates PKA/CREB signaling, reversing neuronal damage.
Gao et al. [78] found that CDPs modulate the gut-brain axis, reduce inflammation, and support NSC function.
Li et al. [79] clinical trials showed reduced T-tau, TNF, IL-1 in AD patients, improving MMSE scores.
Vascular Dementia (VD):
Zhang et al. [80] demonstrated that Cistanche glycosides promote cytoskeletal regeneration, improving cognition in VD models [81].
Parkinson's Disease (PD):
Liang et al. [82] found that echinacoside activates ERK signaling, upregulates GDNF, and inhibits microglial activation, protecting dopaminergic neurons.
Xu et al. [83] used molecular docking to show that β-sitosterol targets Nrf2/SOD1, offering antioxidant-based neuroprotection.
🧠 These findings underscore Cistanche deserticola's potential in multi-pathway neuroprotection, involving Wnt/β-catenin, P2X7R/CX3CR1, HIF-1α, LPCAT3, PKA/CREB, and Nrf2 pathways.
