A nationwide retrospective cohort study conducted in Taiwan has found that Chinese herbal medicine significantly reduces overall mortality in HIV-infected patients with osteoporosis or fractures. This study utilized data from the National Health Insurance Research Database and included 498 patients diagnosed with both HIV and osteoporosis or fractures.
A total of 160 patients were classified as Chinese herbal medicine users and 338 as non-users. To minimize confounding factors, a 1:1 propensity score matching was employed, resulting in 149 Chinese herbal medicine users matched to 149 non-users based on age, gender, and time from HIV diagnosis to osteoporosis/fracture diagnosis. Patients receiving Chinese herbal medicine had a notably lower risk of all-cause mortality than non-users [1].
The study employed association rule mining and network analysis to identify Chinese herbal prescription patterns. Chuan Xiong Cha Tiao San was the most commonly prescribed herbal formula. The second and third most frequent formulas were Liu He Tang and Jia Wei Ping Wei San, respectively. Gan Cao (Glycyrrhiza uralensis Fisch.) was the most commonly used single herb and appeared frequently as a constituent in several of the composite formulas [1].
The primary formulas associated with reduced mortality in the analysis were Chuan Xiong Cha Tiao San, Liu He Tang, Huang Qin Tang, Jia Wei Ping Wei San, and Dang Gui Long Hui Wan. Although initially listed alongside formulas, Gan Cao should be considered separately as it is a single herb rather than a multi-herb formula and was included as a component in most of the formulas listed [1].
Chuan Xiong Cha Tiao San is a classical formula traditionally used to disperse wind and alleviate pain. In Traditional Chinese Medicine (TCM), the term “disperse wind” refers to expelling or relieving pathological factors that manifest suddenly and move quickly. Chuan Xiong Cha Tiao San contains Bo He (Mentha haplocalyx), Chuan Xiong (Ligusticum chuanxiong), Bai Zhi (Angelica dahurica), Qiang Huo (Notopterygium incisum), Xi Xin (Asarum heterotropoides), Jing Jie (Schizonepeta tenuifolia), Fang Feng (Saposhnikovia divaricata), Gan Cao (Glycyrrhiza uralensis), and Lu Cha (Camellia sinensis). Bo He and Jing Jie contribute to the formula's dispersing action, while Chuan Xiong and Bai Zhi are valued for promoting blood circulation and alleviating pain [1].
Gan Cao, often used as a harmonizing herb, also exhibits significant pharmacological properties. In Traditional Chinese Medicine (TCM), a “harmonizing herb” is used to balance and coordinate the effects of other herbs in a formula, promote internal physiological stability, and reduce side effects or toxicity from stronger components. Gan Cao contains glycyrrhizin, which has demonstrated anti-inflammatory, immunomodulatory, and antiviral activities. Gan Cao was used frequently both as a single herb and in combination with complex formulas, reflecting its central role in clinical practice [1].
Liu He Tang is used for clearing heat and transforming phlegm. In Traditional Chinese Medicine (TCM), “clearing heat” refers to eliminating pathological heat, which can manifest as inflammation, fever, infection, irritability, redness, swelling, or excessive metabolic activity. Liu He Tang contains the following ingredients: Ren Shen (Panax ginseng), Bai Zhu (Atractylodes macrocephala), Bai Bian Dou (Dolichos lablab), Gan Cao (Glycyrrhiza uralensis), Hou Po (Magnolia officinalis), Sha Ren (Amomum villosum), Xing Ren (Prunus armeniaca), Fu Ling (Poria cocos), Mu Gua (Chaenomeles speciosa), Huo Xiang (Agastache rugosa), and Ban Xia (Pinellia ternata). In the context of this study, its relevance likely lies in managing systemic inflammation and modulating gastrointestinal symptoms that may accompany antiretroviral therapy or opportunistic infections [1].
Huang Qin Tang, another frequently prescribed formula, is traditionally used to clear internal heat and harmonize the intestines. It contains Huang Qin, Bai Shao (Paeonia lactiflora), Da Zao (Ziziphus jujuba), and Gan Cao. Its inclusion in the therapeutic regimen is noteworthy due to its active flavonoids such as baicalin and wogonin, which have been shown to inhibit inflammatory cytokine production and protect mucosal immunity [1].
Jia Wei Ping Wei San is a modified version of Ping Wei San that incorporates herbs to address concurrent heat or damp-heat conditions. Jia Wei Ping Wei San contains Cang Zhu (Atractylodis rhizoma), Hou Po (Magnolia officinalis), Chen Pi (Citrus reticulata), Qing Pi (Citrus reticulata viride), Mai Ya (Hordeum vulgare), Shen Qu (Massa fermentata), Sha Ren (Amomum villosum), Xiang Fu (Cyperus rotundus), Chuan Xiong (Ligusticum chuanxiong), Gan Cao (Glycyrrhiza uralensis), Sheng Jiang (Zingiber officinale), and Da Zao (Ziziphus jujuba). This formula is used to improve spleen function and resolve dampness, which are common underlying patterns in chronic illness and digestive dysfunction seen in HIV-infected individuals [1].
Dang Gui Long Hui Wan is a detoxifying and purgative formula. Dang Gui Long Hui Wan contains Dang Gui (Angelica sinensis), Long Dan Cao (Gentiana scabra), Lu Hui (Aloe ferox), Qing Dai (Indigo naturalis), Zhi Zi (Gardenia jasminoides), Huang Lian (Coptis chinensis), Huang Qin (Scutellaria baicalensis), Huang Bai (Phellodendron amurense), Da Huang (Rheum palmatum), Mu Xiang (Aucklandia lappa), She Xiang (Moschus moschiferus), Sheng Jiang (Zingiber officinale), and Shi Chang Pu (Acorus gramineus). These herbs contribute to anti-inflammatory and liver-clearing actions, with Dang Gui also promoting blood generation and circulation [1].
Inhibition of osteoclast differentiation resulting in the suppression of bone resorption is one of the potential therapeutic targets for anti-osteoporotic and anti-fracture activities. Several active phytochemicals in the prescribed formulas may contribute to these mechanisms. Ferulic acid, present in Ligusticum sinense and Angelica sinensis, has been shown to suppress RANKL-induced osteoclastogenesis through inhibition of the NF-κB signaling pathway. This results in a downregulation of osteoclast-related gene expression and decreases bone resorption activity [1].
Gallic acid, found in herbs used in Liu He Tang and Huang Qin Tang, exhibits antioxidant and anti-inflammatory activities. It attenuates osteoclast formation and function, thus helping preserve bone mass. Apigenin, a flavonoid found in Bo He, contributes to osteoclast apoptosis and the inhibition of inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6. Quercetin, identified in Dang Gui and other botanical constituents, promotes osteoblast differentiation and inhibits bone resorption. Wogonin and baicalin, major flavonoids in Huang Qin, have both shown anti-inflammatory properties by modulating cytokine profiles and reducing oxidative stress [1].
These formulas collectively include bioactive compounds with well-characterized molecular targets. Their synergy and inclusion in multi-herb prescriptions support the hypothesis that Chinese herbal formulations provide multidimensional mechanisms of action against bone degradation and systemic inflammation in HIV-infected individuals with skeletal complications.
Chinese herbal medicines were administered by licensed traditional Chinese medicine doctors in Taiwan and included both single herbs and classical formulas. All herbal products were manufactured in compliance with pharmaceutical Good Manufacturing Practice standards to ensure quality and consistency. Patients began Chinese herbal medicine treatment within one year of their osteoporosis or fracture diagnosis and maintained usage consistently throughout the follow-up period.
Multivariate Cox regression models adjusted for comorbidities and antiretroviral therapy status were applied to assess the relationship between Chinese herbal medicine use and mortality. Antiretroviral usage did not significantly differ between groups, and was not a significant predictor of mortality in the matched cohort. Kaplan-Meier survival analysis showed a higher cumulative survival rate in the Chinese herbal medicine group over the follow-up period [1].
This study, conducted by researchers from China Medical University Hospital and other affiliated institutions, is the first large-scale, population-based study to demonstrate the survival benefits of Chinese herbal medicine in HIV-infected patients with skeletal complications. The findings suggest that the integration of Chinese herbal medicine into standard HIV care may enhance long-term outcomes in patients at risk for or living with osteoporosis or fracture-related morbidity. Further randomized controlled trials are necessary to validate these findings and clarify the pharmacodynamic interactions between specific herbs and conventional therapies.
1. Mao-Wang Ho et al., "Chinese Herbal Medicine Usage Reduces Overall Mortality in HIV-Infected Patients With Osteoporosis or Fractures," Frontiers in Pharmacology 12 (2021): Article 593434.
