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Inflammatory Biomarkers: An Important Tool for Herbal Drug Discovery
Published in Mahfoozur Rahman, Sarwar Beg, Mazin A. Zamzami, Hani Choudhry, Aftab Ahmad, Khalid S. Alharbi, Biomarkers as Targeted Herbal Drug Discovery, 2022
Mahfoozur Rahman, Ankit Sahoo, Mohammad Atif, Sarwar Beg
Gambogic acid (GA), which derives from Garcinia hanburyi and Garcinia more/la, is a polyprenylated xanthone containing resin. It is used as a complementary and alternative medicine in South-East Asia. GA can be seen as successful anti-arthritis molecules that restrict the secretion of IL-lb and TNF. Intraperitonial GA administration in early and late stage of arthritis to AIA rats at 4 Ig/g body weight (BW) every day may result in the total removal of inflammation and cellular proliferation.
Novel Drug Delivery Systems for Nutraceuticals with Anticancer Properties
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Priyanka Bhatt, Imran Vhora, Rohan Lalani
Other drug molecules that have shown beneficial outcomes in clinical trials include resveratrol and gambogic acid. Multiple clinical trials have been carried out on micronized resveratrol [101], and it has been demonstrated that micronization enhanced the oral bioavailability by 3.6-fold as compared to non-micronized resveratrol. This in turn, improved the therapeutic effects in hepatic malignant tissues [102] and in Phase II study of multiple myeloma in combination with bortezomib [103]. This opens the possibility for nanosizing of the resveratrol as well as other nutraceuticals with lower oral bioavailability. Gambogic acid solution for IV injection is in clinical trials in China for solid tumors and hematological malignancies. In Phase I tolerability study with gambogic acid solution, liver dysfunction and pain were the dose-limiting toxicities [104]. In Phase II efficacy studies on patients with advanced solid tumor who were not receiving any treatment or were not sensitive to previous conventional chemotherapy, gambogic acid solution showed improved disease control rates compared to control arm [105]. Lyc-O-Mato (lycopene soft gel capsules by Lycored Natural Products Industries, Israel) is lycopene in which the particle size is controlled below 3 μ to enhance the bioavailability [106]. It has shown enhanced bioavailability in clinical trials compared to raw tomato [97,98] and has demonstrated reduced prostate cancer growth in clinical trials [99]. So, efforts can be directed toward nanoformulations of these molecules to improve the bioavailability and overcome toxicities.
Antipsoriatic Medicinal Plants
Published in José L. Martinez, Amner Muñoz-Acevedo, Mahendra Rai, Ethnobotany, 2019
José Luis Ríos, Guillermo R. Schinella, Isabel Andújar
Among the phenolics, gambogic acid, the main active compound isolated from the resin of the Garcinia hanburyi Hook.f. (Clusiaceae) tree, and honokiol, a biphenolic neolignan isolated from Magnolia officinalis Rehder & E.H.Wilson (Magnoliaceae), have been reported to have anti-angiogenic and anti-inflammatory properties through the inhibition of the transcription factor NF-κB (Wen et al. 2014a, 2015). Gambogic acid and honokiol (Fig. 9.2) were tested in vitro and in vivo: in vitro, gambogic acid inhibited the proliferation of the human keratinocyte cell line HaCaT (IC50 = 0.09 μM) and it was also demonstrated to be active in human umbilical vein endothelial cells (HUVEC) by inhibiting TNF-α-induced activation of NF-κB, both processes being highly active in psoriatic patients. Honokiol also inhibited TNF-α-induced NF-κB activation in HUVEC and decreased the ratio of Th1/Th2-expression CD4+ T cells.
Gambogic acid-loaded PEG–PCL nanoparticles act as an effective antitumor agent against gastric cancer
Published in Pharmaceutical Development and Technology, 2018
Dinghu Zhang, Zhengyun Zou, Wei Ren, Hanqing Qian, Qianfeng Cheng, Liulian Ji, Baorui Liu, Qin Liu
Gambogic acid (GA) was the main active component of gamboge extracted from Garcinia hanburyi a tree native to Southeast Asia. It displayed anti-inflammatory, anti-oxidant, antiviral and anti-infectious effects (Yao et al. 2014). In addition, GA exhibited a broad spectrum of antitumor activity in vitro and in vivo, which was mainly attributed to the downregulation of telomerase and induction of apoptosis (Huang et al. 2011) in a wide range of tumor cells, such as human gastric carcinoma, human lung carcinoma and human hepatoma cells (Wang et al. 2010). Our previous study suggested that GA reversed docetaxel resistance in gastric cancer cells by inhibiting the apoptosis-related gene surviving (Wang et al. 2008). Shi et al. showed that GA triggered cellular apoptosis by proteasome inhibition-induced caspase activation (Shi et al. 2015). However, the clinical use of GA as an antitumor agent was restricted by poor aqueous solubility, rapid plasma clearance and systemic toxicities (Yao et al. 2014).
A novel redox/pH dual-responsive and hyaluronic acid-decorated multifunctional magnetic complex micelle for targeted gambogic acid delivery for the treatment of triple negative breast cancer
Published in Drug Delivery, 2018
Mang Mang Sang, Fu Lei Liu, Yang Wang, Ren Jie Luo, Xiao Xian Huan, Ling Fei Han, Zhong Tao Zhang, Feng Feng, Wei Qu, Wenyuan Liu, Feng Zheng
Gambogic acid (GA) is a recently explored polyprenylated xanthene, which is the main small molecule active ingredient of gamboge resin that is exuded from the Garcinia hanburyi tree in Southeast Asia has multiple therapeutic actions and was been used for hundreds of years in China (Auterhoff et al., 1962; Wang et al., 2013). Both in vitro and in vivo studies have demonstrated that GA has significant anticancer activity, against numerous types of human cancer, including prostate, gastric carcinoma, hepatocarcinoma, lung cancer, and breast carcinoma (Yang et al., 2007; Qi et al., 2008; Doddapaneni et al., 2016). It also has been approved for phase-II clinical trials by the Chinese Food and Drug Administration (Gu et al., 2009). But the poor water solubility (<5 ppm) and short biological half-life (less than 1 hour in dogs and less than 20 minutes in rats) (Liu et al., 2017) were proved to the major hurdle for GA clinical application.
N-octyl-N-arginine-chitosan micelles for gambogic acid intravenous delivery: characterization, cell uptake, pharmacokinetics, and biodistribution
Published in Drug Development and Industrial Pharmacy, 2018
Fan Yu, Fuguang Jiang, Xinhui Tang, Bochu Wang
Chitosan (CS, deacetylation degree >90%; M wt. = 100 kDa) was purchased from Jingke Biochemical Co. Ltd. (Zhejiang, China), L-arginine was obtained from Shanghai Huixing Biochemistry Reagent Ltd. Co. (Shanghai, China), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC·HCl) and N-hydroxy succinimide (NHS) were purchased from Shanghai Medpep Co. Ltd (Shanghai, China). Gambogic acid (99.7%) was obtained from China Pharmaceutical University. All other reagents were of analytical grade and used without further purification.