Hemp (Cannabis sativa L.) is used for medicinal purposes owing to its anti-inflammatory and antioxidant activities. We evaluated the protective effect of nanovesicles isolated from hemp plant parts (root, seed, hemp sprout, and leaf) in dextran sulfate sodium (DSS)-induced colitis in mice. The particle sizes of root-derived nanovesicles (RNVs), seed-derived nanovesicles (SNVs), hemp sprout-derived nanovesicles (HSNVs), and leaf-derived nanovesicles (LNVs) were within the range of 100–200 nm as measured by nanoparticle tracking analysis. Acute colitis was induced in C57BL/N mice by 5% DSS in water provided for 7 days. RNVs were administered orally once a day, leading to the recovery of both the small intestine and colon lengths. RNVs, SNVs, and HSNVs restored the tight (ZO-1, claudin-4, occludin) and adherent junctions (E-cadherin and α-tubulin) in DSS-induced small intestine and colon injury. Additionally, RNVs markedly reduced NF-κB activation and oxidative stress proteins in DSS-induced small intestine and colon injury. Tight junction protein expression and epithelial cell permeability were elevated in RNV-, SNV-, and HSNV-treated T84 colon cells exposed to 2% DSS. Interestedly, RNVs, SNVs, HSNVs, and LNVs reduced ALT activity and liver regeneration marker proteins in DSS-induced liver injury. These results showed for the first time that hemp-derived nanovesicles (HNVs) exhibited a protective effect on DSS-induced gut leaky and liver injury through the gut–liver axis by inhibiting oxidative stress marker proteins.

Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 μg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.

Aloe-derived nanovesicles exhibit anti-oxidant and anti-inflammatory effects, and decrease intestinal epithelial permeability with enhanced expression of TJ and AJ proteins in an ulcerative colitis model, potentiating their use in treatment of IBD.

Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.

Osteoporosis is characterized by low bone mass and elevated structural deterioration of the bone tissue, resulting in bone weakness with an increased risk of fracture. Considering biological activities of various phytochemicals extracted from apples, we herein demonstrated the potential antiosteoporotic effects of apple-derived nanovesicles (apple NVs) using osteoblastic MC3T3-E1 cells. Apple NVs significantly stimulated the growth of MC3T3-E1 cells. The cellular alkaline phosphatase (ALP) activity was significantly upregulated in the 5 μ g/mL apple NVs-treated group. In addition, the concentrarion of mineralized nodules was significantly increased in the apple NVs-treated groups. Furthermore, apple NVs increased the expression of the genes and proteins associated with osteoblast growth and differentiation, such as Runx2, ALP, OPN, and BMP2/4, which further activated ERK- and JNK-related mitogen-activated protein kinase signaling. These results demonstrate that apple NVs have a potential to prevent osteoporosis by promoting osteoblastogenesis in osteoblastic MC3T3-E1 cells through regulating the BMP2/Smad1 pathways.