Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy

Abstract

Background Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed. Results For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (− 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis. Conclusion Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.

Emergence of Edible Plant-Derived Nanovesicles as Functional Food Components and Nanocarriers for Therapeutics Delivery: Potentials in Human Health and Disease

“…Oat bran meal was dissolved in PBS and then incubated in a 37 °C water bath for 30 min for supernatant collection and subsequent centrifugation [ 29 ]. Root vegetables, such as carrot [ 30 ], garlic [ 31 , 32 , 33 ], ginger [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], ginseng [ 42 , 43 ], and turmeric [ 44 ], and leafy vegetables including cabbage [ 45 ], were prepared similarly to fruits by blending them with or without additional PBS pre- or post-grinding.…”

“…Ginger-derived nanovesicles also contained PA in a high percentage (~40%) along with plant lipids such as digalactosyldiacylglycerol (DGDG) (30~40%) and monogalactosyldiacylglycerol (MGDG) (~20%) [ 34 , 39 ]. Turmeric, which belongs to the ginger family, also showed high DGDG (~42%) and MGDG (~12%) along with PA (~20%) and phosphatidylcholine (PC) (~16%) [ 44 ].…”

“…Based on these findings, it is conceivable that oral administration of PDNVs and subsequent absorption may be affected by changes in pH of the gastrointestinal tract. Indeed, in vitro setting mimicking digestion conditions showed PBS and intestine-like solution resulted in a slight negative charge in PDNVs and a slight positive charge in PDNVs in acid solution [ 34 , 44 ]. Currently, the absence of evidence leaves this open to discussion.…”

“…The results showed the ginger-derived nanovesicles were stable in those solutions with a slight reduction in size and zeta potential changed according to the surrounding pH: negative charge in the PBS and intestine-like solution; and slightly positively charged in the stomach-like solution [ 34 ]. Turmeric-derived nanovesicles also maintained nano-scale size under different pH solutions with their size increased, undergoing similar zeta potential changes as ginger-derived nanovesicles [ 44 ]. These collectively suggest PDNVs would survive a harsh environment in the GI tract when orally consumed in food form or purified form due to their membrane versatility.…”

Extracellular Vesicles: The Next Generation Theranostic Nanomedicine for Inflammatory Bowel Disease

“…163 Additionally, oral administration of turmericderived exosome-like nanovesicles can ameliorate mouse colitis and accelerate colitis resolution via decreasing the expressions of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and increasing the levels of the antioxidant gene, heme oxygenase-1 (HO-1) in mice colitis models. 164 Unfortunately, clinical trials are limited to the efficacy and safety of PDENs for IBD patients. The Therapeutic Effect of Milk-Derived Exosomes on IBD Milk-derived exosomes play an important role in the development of the digestive tract, which regulate intercellular signaling, inflammation and immune response, thus protecting against stress and various disease conditions including IBD.…”