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Natural Product Communications
Anti-inflammatory Potential of Silk Sericin
2013 Vol. 8 No. 4 501 - 504
Pornanong Aramwita,*, Pasarapa Towiwatb and Teerapol Srichanac a
Bioactive Resources for Innovative Clinical Applications Research Unit and Department of Pharmacy Practice, and bDepartment of Pharmacology and Physiology Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand c Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkla, 90110, Thailand
[email protected] Received: December 3rd, 2012; Accepted: February 28th, 2013
Silk sericin was found to suppress the production of pro-inflammatory cytokines, which are related to the inflammatory reaction. The objectives of this study were to investigate the anti-inflammatory effect of sericin in vivo using the carrageenan-induced rat edema model and changes in the histology of tissues. The effects of sericin on the expression of COX-2 and iNOS were also evaluated. Sericin solutions at 0.004-0.080 mg/mL were applied topically to the top of the hind paw and carrageenan (1.0 mg) was injected subcutaneously to the plantar surface of the right hind paw. Our results indicated that sericin significantly reduced the inflammation in rats’ paw compared with the negative control (water and acetone) and its effect at 0.080 mg/mL was only slightly lower than that of 1.0% w/v indomethacin. Similar numbers of polymorphonuclear and macrophage cells were found in rats’ tissue treated with indomethacin and sericin solution, while the numbers were significantly higher in their absence. The gene expression results by RT-PCR showed that the COX-2 and iNOS genes were down-regulated in samples treated with sericin in a dose dependent manner. These data indicated that the anti-inflammatory properties of sericin may be partly attributable to the suppression of the COX-2 enzyme and nitric oxide production. Keywords: Sericin, Inflammation, Cyclooxygenase-2, Carrageenan.
Sericin, a degumming protein from silk cocoons, has been discarded in nature for decades. However, recently it has been receiving much attention and is being investigated for its biological activities [1-6]. The actions of silk sericin on suppressing production of pro-inflammatory cytokines has been reported [7, 8], but not for any anti-inflammatory action. Zhaorigetu et al. reported earlier that sericin significantly suppressed the elevated expressions of c-fos, c-myc and COX-2 in normal epidermis induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) application [6], which related to anti-inflammation activity. However, a direct and doserelated anti-inflammatory property of this activity has never been investigated. Inflammation is essentially a protective process that preserves the integrity of the organisms against physical, chemical and infective insults [9]. Moreover, the inflammatory response to several insults can lead to normal tissue damage [10]. The in vivo acute inflammation model of carrageenan-induced paw edema has been frequently used to assess the anti-inflammatory effect of natural products. During inflammation induced by carrageenan, several mediators are released, such as histamine and serotonin, as well as prostaglandins, protease and lysosome [11, 12]. The inflammatory response is usually quantified by the increase in paw size (edema) and is modulated by inhibitors of specific molecules within the inflammatory cascade, such as nonsteroidal anti-inflammatory drugs (NSAIDs) [13]. Several signals and enzymes are involved in the inflammatory process. Cyclooxygenase (COX) is a key rate-limiting cellular enzyme involved in the synthetic pathway of prostaglandins and thromboxane from arachidonic acid [14]. It plays important roles in host inflammatory and stress responses. COX-2 is an inducible immediate-early gene product whose synthesis in cells can be upregulated by either mitogenic or inflammatory stimuli [14,15a]. It also plays an important role in skin inflammation, cell proliferation and skin tumor promotion [15b]. Nitric oxide (NO) is a signaling
molecule that regulates cellular functions in both physiological and pathophysiological conditions in the human body [16a]. NO modulates immune responses and the inflammatory process during inflammation, especially inducible nitric oxide synthase (iNOS), which is induced in response to cytokines and bacterial products in inflammatory and tissue cells, and its overproduction is associated with the pathophysiology of various inflammatory diseases [6b,17], COX-2 and NOS were selected to be measured as indicators for the anti-inflammatory activity of sericin. Compounds that inhibit COX-2 or iNOS expression normally exhibit anti-inflammatory properties [18,19]. In this study, we assessed the anti-inflammatory reaction of silk sericin compared with indomethacin (IND, a NSAID) using the carrageenan-induced rat edema model. The responses of various cells associated with inflammatory responses from rats’ tissues were evaluated by histological examinations. We also investigated the effects of sericin solution on the expression of COX-2 and iNOS as these may contribute to any beneficial clinical effects of sericin. Intraplantar injection of carrageenan to rats resulted in severe discernible inflammation and a significant increase in the mean volume of the control paws (sterile water or acetone treated) compared with the positive control (IND-treated) paws. Our results indicated that pre-treatment of rats with sericin solution at all concentrations inhibited (50% inhibition or more) the carrageenaninduced increase in the edema volume of the paws (Table 1). As shown in Table 1, carrageenan injection at the test dose exhibited maximum inflammation at approximately 3 h and then gradually decreased. Sericin at a high concentration (0.080 mg/mL in water) significantly inhibited the inflammation induced by carrageenan. All concentrations of sericin significantly inhibited the inflammation 3 h after injection of carrageenan compared with the
502 Natural Product Communications Vol. 8 (4) 2013
Aramwit et al.
Table 1: Average rats’ paw volume of the tested materials in carrageenan-induced paw edema. Treatments
0 h (at the time of carrageenan injection) 0.05 0.02 0.03 0.01 0.04 0.02 0.04 0.01 0.05 0.02 0.05 0.01 0.03 0.02 0.02 0.02
Acetone 1% IND Water Sericin 0.08 mg/mL Sericin 0.04 mg/mL Sericin 0.02 mg/mL Sericin 0.01 mg/mL Sericin 0.004 mg/mL a
1h 0.18 0.04 0.06 0.05a 0.25 0.03 0.10 0.03a 0.18 0.07 0.15 0.04 0.12 0.03a 0.16 0.05
Paw Volume (mL) SD 2h 3h 0.38 0.04 0.55 0.06 0.03 0.08c 0.08 0.09c 0.33 0.03 0.49 0.08 0.13 0.05b 0.08 0.04c b 0.13 0.09 0.10 0.09a 0.16 0.06a 0.18 0.05b 0.19 0.05 0.24 0.06b 0.19 0.04a 0.21 0.06a
4h 0.45 0.07 0.07 0.08c 0.36 0.03 0.09 0.02b 0.12 0.12 0.09 0.06a 0.11 0.09a 0.22 0.09
5h 0.35 0.07 0.04 0.05c 0.32 0.04 0.14 0.02 0.15 0.12 0.10 0.07a 0.15 0.07 0.23 0.09
6h 0.23 0.09 -0.01 0.06a 0.26 0.04 0.06 0.02 0.16 0.15 0.10 0.07 0.15 0.09 0.25 0.09
indicates significant difference at p
