Research Article: The Anti-Inflammatory, Phytoestrogenic, and Antioxidative Role of Labisia pumila in Prevention of Postmenopausal Osteoporosis

Date Published: March 15, 2012

Publisher: Hindawi Publishing Corporation

Author(s): M. E. Nadia, A. S. Nazrun, M. Norazlina, N. M. Isa, M. Norliza, S. Ima Nirwana.


Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone-formation and increase in bone-resorption activity. Estrogen is able to suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and TNF-α. This is why these cytokines are elevated in postmenopausal women. Studies have shown that estrogen reduction is able to stimulate focal inflammation in bone. Labisia pumila (LP) which is known to exert phytoestrogenic effect can be used as an alternative to ERT which can produce positive effects on bone without causing side effects. LP contains antioxidant as well as exerting anti-inflammatory effect which can act as free radical scavenger, thus inhibiting TNF-α production and COX-2 expression which leads to decline in RANKL expression, resulting in reduction in osteoclast activity which consequently reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and antioxidative properties that make LP an effective agent against osteoporosis.

Partial Text

Plant has been one of the sources of medicine to treat various illnesses and diseases since ancient time. In the early 19th century, when chemical analysis first became available, scientists began to extract and modify the active ingredients from plants which later led to wide development of natural or traditional medicine that was mostly passed on orally from one generation to another. More than 35,000 plant species have been reported to be used in various human cultures around the world for their medical purposes [1]. Traditional medicine has been defined by the World Health Organization (WHO) as “health practices, approaches, knowledge and beliefs incorporating plant, animal and mineral-based medicines, spiritual therapies, manual techniques and exercises, applied singularly or in combination, to treat, diagnose and prevent illnesses or maintain well-being” [2].

Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue. According to the National Institute of Health, osteoporosis is a skeletal disease which involves decline in mass and density which later leads to fracture [31]. Women, especially postmenopausal women, are more likely to develop osteoporosis than men due to tremendous decline in estrogen during menopause which will lead to decline in bone formation and increase in bone-resorption activity [32]. Osteoporosis is attributed to various factors, and there are evidences that inflammation also exerts significant influence on bone turnover, inducing osteoporosis [33, 34]. According to studies by Lorenzo and Manolagas and Jilka, certain pro-inflammatory cytokines play potential critical roles both in the normal bone remodeling process and in the pathogenesis of osteoporosis [34, 35]. For example, interleukin- (IL-) 6 promotes osteoclasts differentiation and activation [36]. IL-1 is another potent stimulator of bone resorption [37] that has been linked to the accelerated bone loss seen in postmenopausal osteoporosis [38].

LP which has been opposed to exert phytoestrogen property can be used as an alternative to estrogen replacement therapy (ERT) in postmenopausal inflammation-induced osteoporosis. In contrast to ERT which can cause many harmful side effects, LP which originated from natural resources will not cause any side effect, if taken within its safe therapeutic dose. Toxicity testing of LP which was done by the Herbal Medicine Research Centre of Institute of Medical Research has shown that LD50 is safe at more than 5.0 g/kg [51]. LP extract was found to exhibit no-adverse-effect level (NOAEL) at the dose of 50 mg/kg in subacute toxicity study [52], 1000 mg/kg in subchronic toxicity study [53], and 800 mg/kg in reproductive toxicity study [51]. Therefore, LP is safe to be given at high dose as long as it does not outweigh the toxic dose.

Based on previous studies, LP has been shown to exhibit antioxidative properties due to the presence of flavanoids, ascorbic acid, beta-carotene, anthocyanin, and phenolic compounds [66, 67]. According to Norhaiza et al. [68], there were positive correlations between the antioxidant capacities and the antioxidant compounds of LP extract with β-carotene having the best correlation, followed by flavonoid, ascorbic acid, anthocyanin, and phenolic content. β-carotene is one of the basic constituent of antioxidative effect. The chemical abilities of β-carotene to quench singlet oxygen and to inhibit peroxyl free radical actions are well established [69]. Flavonoid has been shown to be highly effective scavenger of free radicals that are involved in diseases such as osteoporosis and rheumatism which is associated with aging due to oxidative stress [70]. Anthocyanin and phenolic on the other hand, not only play a role as antioxidative agents, but also as anti-inflammatory agents [71–73]. These antioxidative and anti-inflammatory properties of LP extract explained the effectiveness of this medicinal plant against various diseases such as osteoporosis, rheumatism, and women sexual function.