Vascular-Dependent Diseases and the TCM Methods of Activating Blood to Resolve Stasis and Dissolving Phlegm to Disperse Nodules
Blood vessels are widely distributed throughout every tissue of the body. The human body depends on vessels to deliver nutrients and oxygen and to expel waste, so as to maintain normal metabolism and life activities. Under physiological conditions, angiogenesis does not occur except in certain specific organs and tissues, such as embryonic tissue in growth and development, the ovary during ovulation and corpus luteum formation, the endometrium during the menstrual cycle, and tissues undergoing wound healing. Even in these cases, angiogenesis is tightly regulated, taking place only for a short time before being suppressed and returning to a quiescent state.
Under certain pathological conditions, however—such as arthritis, diabetic retinopathy, and the growth and metastasis of malignant tumors—angiogenesis becomes a sustained, uncontrolled process. This disordered vascular growth promotes the occurrence and progression of disease. Abnormal vascular growth and function are hallmarks of cancer, ischemic diseases, and inflammatory diseases, which led the medical community to propose the now widely accepted concept of “angiogenesis-dependent diseases.”
Some drugs in modern medicine are designed precisely against this pathological feature. Many targeted agents—for example bevacizumab, ramucirumab, sorafenib, sunitinib, lenvatinib, apatinib, regorafenib, and cabozantinib—act on tumors by inhibiting angiogenesis, thereby controlling tumor growth.
Do traditional Chinese medicines contain anything similar? The answer is yes. Certain blood-activating stasis-resolving herbs and phlegm-dissolving nodule-dispersing herbs all exhibit, to varying degrees, an inhibitory effect on angiogenesis.
Among blood-activating stasis-resolving herbs are Danshen (Salvia miltiorrhiza), Ezhu (Curcumae Rhizoma), Sanleng (Sparganii Rhizoma), Chishao (Paeoniae Rubrae Radix), Yujin (Curcumae Radix), Jianghuang (Curcumae Longae Rhizoma), Tubiechong (Eupolyphaga/Steleophaga), and Banmao (Mylabris). It should be noted, however, that not all blood-activating stasis-resolving herbs inhibit angiogenesis; some of them, on the contrary, promote it—for example Danggui (Angelicae Sinensis Radix), Chuanxiong (Chuanxiong Rhizoma), Jixueteng (Spatholobi Caulis), Tao ren (Persicae Semen), and Niuxi (Achyranthis/Cyathulae Radix). With rational formula composition, however, the pro-angiogenic effect of such herbs can be avoided.
Compared with Western anti-angiogenic drugs, blood-activating stasis-resolving Chinese herbs are milder in nature, have fewer side effects, and exert a bidirectional regulatory effect: in small doses they activate blood, unblock the collaterals, and promote repair, while only in large doses or in multi-herb combinations do they inhibit angiogenesis.
Besides blood-activating stasis-resolving herbs, many phlegm-dissolving nodule-dispersing Chinese medicines have been shown to lower tumor VEGF and MMP-2/MMP-9, downregulate the Wnt/PI3K/Akt pathway, reduce intratumoral microvessel density, and inhibit HUVEC proliferation and tube formation. Shancigu (Cremastrae/Appendiculata Pseudobulbus), Zhebeimu (Fritillariae Thunbergii Bulbus), Tubeimu (Bolbostematis Rhizoma), Xiakucao (Prunellae Spica), Jiegeng (Platycodi Radix), Banxia (Pinelliae Rhizoma), Tiannanxing (Arisaematis Rhizoma), Haizao (Sargassum), Kunbu (Eckloniae/Laminariae Thallus), Zaojiaoci (Gleditsiae Spina), Jiangcan (Bombyx Batryticatus), and Lufengfang (Nidus Vespae) all belong to the phlegm-dissolving nodule-dispersing category in traditional Chinese medicine; modern pharmacological research indicates that these herbs can inhibit neovascularization.
From this perspective, the emphasis in traditional TCM formulas on using blood-activating stasis-resolving and phlegm-dissolving nodule-dispersing strategies for tumors does carry a certain rationale.