Perspectives on medicinal properties of plumbagin and its analogs

Abstract

Plumbagin is one of the simplest plant secondary metabolite of three major phylogenic families viz. Plumbaginaceae, Droseraceae, and Ebenceae, and exhibits highly potent biological activities, including antioxidant, antiinflammatory, anticancer, antibacterial, and antifungal activities. Recent investigations indicate that these activities arise mainly out of its ability to undergo redox cycling, generating reactive oxygen species and chelating trace metals in biological system. The compound is endowed with a property to inhibit the drug efflux mechanism in drug-resistant bacteria, thereby allowing intracellular accumulation of the potent drug molecules. An interesting bioactivity exhibited by this compound is the elimination of stringent, conjugative, multidrug-resistant plasmids from several bacterial strains including opportunistic bacteria, such as Acinetobacter baumannii. Moreover, plumbagin effectively induces apoptosis and causes cell cycle arrest, which is, in part, due to the inactivation of NF-κB in cancer cells. Therefore, it has been suggested that designing "hybrid drug molecules" of plumbagin by combining it with other appropriate anticancer agents may lead to the generation of novel and potent anticancer drugs with pleiotropic action against human cancers. This comprehensive review is an attempt to understand the chemistry of plumbagin and catalog its biological activities reported to date.

Plumbagin enhances TRAIL-induced apoptosis of human leukemic Kasumi-1 cells through upregulation of TRAIL death receptor expression, activation of caspase-8 and inhibition of cFLIP

“…Plumbagin (5-hydroxy-2-methyl-1,4-napthoquinone), which is isolated from the roots of the medicinal plant Plumbago zeylanica L, has been safely used for centuries in Indian Ayurvedic and Oriental medicine for the treatment of various ailments (10,11). Plumbagin and its analogs exhibit a variety of potent pharmacological and biological activities including anti-microbial (12,13), anti-malarial (14), anti-inflammatory (15), anti-atherosclerotic (16), anti-diabetic (17) and neuroprotective (18) effects.…”

Plumbagin inhibits cell proliferation and promotes apoptosis in multiple myeloma cells through inhibition of the PI3K/Akt-mTOR pathway

“…Plumbagin, a natural naphthoquinone compound, is the primary active component of the traditional Chinese medicine Baihua Dan (6). Baihua Dan has been administered clinically in China for centuries, and the effects of plumbagin include anti-inflammatory (7), antiseptic (8) and anti-protozoa (9) effects.…”

Plant-derived anticancer agents: a promising treatment for bone metastasis

“…The properties are exerted through a variety of mechanisms, including signal transducer and activator of transcription 3 (STAT3) activation, 15 induction of p53 and c-Jun N-terminal kinase expression in human nonsmall-cell lung cancer cells, 16 inhibition of the nuclear factor-kB (NF-kB)/Bcl-2 pathway 12 and by downregulating the expression of the chemokine receptor CXCR4. 17 The antitumor effects of plumbagin have been shown in several cancers including squamous cell carcinoma, 18 leukemia 19 and myeloma, 15 as well as breast, 17,20 ovarian, 21 pancreatic, 22 lung, 23 liver 24 and cervical cancers. 25 In bone, breast cancer cells increase bone resorption by producing factors such as the parathyroid hormone-related protein (PTHrP) and interleukins that stimulate the osteoblasts and increase the production of the receptor activator of NF-kB (RANK) ligand (RANKL).…”