Inhibitory Effects of Standardized Boesenbergia pandurata Extract and Its Active Compound Panduratin A on Lipopolysaccharide-Induced Periodontal Inflammation and Alveolar Bone Loss in Rats Haebom Kim, 1, * Changhee Kim, 1, * Kyo Eun Kook, 1 Yanti, 2 Seungmok Choi, 3 Wonku Kang, 3 and Jae-Kwan Hwang 1 1 Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea. 2 Food Technology, Faculty of Biotechnology, Atma Jaya Catholic University, Jakarta, Indonesia. 3 College of Pharmacy, Chung-Ang University, Seoul, Korea. ABSTRACT Periodontitis, an inflammatory disease of the gingival tissue, triggered by microbial-derived elements, such as lipopolysaccharide (LPS), collapses the periodontal tissues and resorbs the alveolar bone. This study evaluated the inhibitory effects of standardized Boesenbergia pandurata extract (BPE) and panduratin A (PAN) on periodontitis-induced inflammation and alveolar bone loss. Sprague-Dawley rats with LPS-induced periodontitis were orally administered BPE (50 and 200 mg/kg/ day) and PAN (20 mg/kg/day) for 8 days. Histological analysis revealed that BPE- and PAN-administered groups showed decreased cell infiltration and alveolar bone resorption. Furthermore, the BPE and PAN significantly alleviated the mRNA and protein expression levels of nuclear factor kappa B (NF-jB), interleukin-1b, matrix metalloproteinase (MMP)-2, and MMP-8. BPE and PAN also inhibited the expression of nuclear factor of activated T cells, cytoplasmic 1, c-Fos, and ostoclastogenesis- related enzymes, including cathepsin K and tartrate-resistant acid phosphatase (ALP). BPE and PAN not only upregulated the osteoblastogenesis-associated markers, such as collagen type I (COL1A1) and ALP, but also increased the ratio of osteopro- tegerin to receptor activator of NF-jB ligand. Collectively, BPE and PAN efficiently prevent destruction of periodontal tissues and stimulating the loss of alveolar bone tissues, strongly indicative of their potential as natural antiperiodontitis agents. KEYWORDS:  alveolar bone  Boesenbergia pandurata Roxb.  gingival tissue  panduratin A  periodontitis INTRODUCTION P eriodontitis is an infectious disease occurring in the periodontal tissue around the teeth. The occurrence of periodontitis is followed by severe inflammation of the gingival tissues and destruction of the alveolar bone, ulti- mately resulting in the loss of teeth. 1 Consequently, the ability to masticate is limited and the quality of personal life is severely affected. In addition, periodontitis not only in- fluences the periodontal tissue, mouth, and teeth, but also contributes to systemic diseases, including Alzheimer’s dis- ease, cardiovascular disease, and diabetes. 2–4 The preven- tion and treatment of periodontitis are crucial issues for maintaining good health, suggesting that the systemic health and quality of life are associated with oral health. Gram-negative oral pathogens, such as Porphyromonas gingivalis, are initiators of periodontitis. The host immune system is activated in response to microbial-derived elements, such as lipopolysaccharide (LPS), antigens, and virulence factors. 5 The inflammation activated by microbial-derived elements in the gingival tissues increases the expression of inflammatory factors (interleukin [IL]-1b and nuclear factor kappa B [NF-jB]). Furthermore, the expression of matrix metalloproteinases (MMPs) is upregulated to destroy com- ponents, including gelatins and collagens, which support the matrix of gingival tissues. 6 Inflammation accelerates the expression of receptor acti- vator of NF-jB ligand (RANKL) from fibroblasts in gingival tissues, leading to osteoclast differentiation. 7 Osteoclasts, responsible for bone resorption, balance on osteoblasts, which form new bone under normal conditions. Periodontitis de- stroys the balance, and the prevailing osteoclasts collapse the alveolar bone. 8 The binding between RANKL and the RANK receptor triggers osteoclast differentiation by activating nu- clear factor of c-Fos and activated T cells, cytoplasmic 1 (NFATc1), which work as transcription factors to regulate the genes involved in osteoclastogenesis. 9 Particularly, NFATc1 has an autoamplification system. As a unique NFAT protein, *These authors equally contributed to this work. Manuscript received 9 December 2017. Revision accepted 17 April 2018. Address correspondence to: Jae-Kwan Hwang, PhD, Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea, E-mail: jkhwang@yonsei.ac.kr or Wonku Kang, PhD, College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea, E-mail: wkang@cau.ac.kr JOURNAL OF MEDICINAL FOOD J Med Food 21 (10) 2018, 961–970 # Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition DOI: 10.1089/jmf.2017.4155 961 Downloaded by 119.198.203.21 from www.liebertpub.com at 10/23/18. For personal use only.