Many natural extracts have been shown to minimize the toxicity of doxorubicin (Dox). Low piperine Piper nigrum L. (Piperaceae) extract (PFPE) is a natural extract containing many types of antioxidants that may reduce Dox toxicities.
To evaluate the effect of PFPE in attenuating the side effects of Dox.
Tumour-bearing Sprague Dawley rats were divided into five groups including normal, vehicle, 100 mg/kg BW of PFPE plus 2 mg/kg BW of Dox (P100 + Dox), 100 mg/kg BW of PFPE plus 2 mg/kg BW of Dox (P200 + Dox) and Dox. Rats were treated with Dox and/or PFPE three times/week for 4 weeks. Tumour burden, blood parameters, weight of internal organs and immunological data were investigated.
The addition of 200 mg/kg PFPE significantly restored the levels of AST from 174.60 ± 45.67 U/L in the Dox group near to normal levels at 109.80 ± 4.99 U/L. The combination of PFPE and Dox also decreased the levels of CXCL7, TIMP-1, sICAM-1 and l-selectin about 1.4-1.6-fold compared to Dox group. Feeding rats with 200 mg/kg BW of PFPE combination with Dox slightly increased Th1 from 161.67 ± 14.28 cells in Dox group to 200.75 ± 5.8 cells meanwhile suppressed Treg from 3088 ± 78 cells in Dox to 2561 ± 71 cells.
This study showed that PFPE ameliorated Dox toxicity in many aspects indicating the role of antioxidant and other substances in the extract on toxicity attenuation. This suggested the using of PFPE may be valuable for Dox treated patients.

Aim: To assess the effect of physical training on the selected parameters of the immune system regarding CD3, CD4, CD8, CD11, CD161, CD45A cell counts in rats treated with N-methyl-N-nitrosourea (MNU). Material and Methods: Thirty-eight female Sprague-Dawley rats were injected intraperitoneally with MNU and were divided into three groups, i.e., sedentary control (SC), the group of moderate-intensity training (MIT) and the group of high-intensity training (HIT). Physical training was supervised immediately after MNU administration and was conducted 5 days per week for 12 weeks on a three-position treadmill. Results: A significant difference was found between SC and training groups in terms of the number of induced tumors per rat (1.57 vs. 0.4, p = 0.05) and in the following lymphocyte subpopulations: CD4+/CD8+ (p = 0.01), CD3−/CD11b+ (p = 0.02), CD3−/CD161+ (p = 0.002), CD3−/CD161− (p = 0.002), CD3+/CD45RA+ (p = 0.003) and CD3−/CD45RA+ (p = 0.005). In terms of the intensity of physical training, the highest efficacy was found for MIT and the following lymphocyte subpopulations: CD3−/CD11b+ (SC vs. MIT, p < 0.001), CD3−/CD161+ (SC vs. MIT, p = 0.002), CD3−/CD161− (SC vs. MIT, p = 0.002), CD3+/CD45RA+ (SC vs. MIT, p = 0.02) and CD3−/CD45RA+ (SC vs. MIT, p < 0.001, MIT vs. HIT, p = 0.02). Furthermore, negative correlations were found between the number of apoptotic cells and CD3−/CD11b (r = −0.76, p = 0.01) in SC and between the number of induced tumors and CD3+/CD8+ (r = −0.61, p = 0.02) and between their volume and CD+/CD8+ (r = −0.56, p = 0.03) in the group of rats undergoing training. Conclusions: Physical training, particularly MIT, affected immune cell function and an altered immune response can be considered a mechanism underlying the effect of exercise on breast cancer development.

Much evidence suggests that gut immunity homeostasis plays a vital role in regulating neuroinflammatory response under ischemic stroke. Acupuncture is an effective treatment for post-stroke rehabilitation. However, little is known about the effect of acupuncture on intestinal injury after stroke. Herein, we observed the intestinal inflammatory response and barrier's impairment of the post-stroke rats to explore the mechanism of electroacupuncture (EA) against cerebral ischemia injury from the brain-gut axis. Rats were randomized to the sham operation group (SHAM), the middle cerebral artery occlusion group (MCAO), and the MCAO plus EA treatment group (MEA). Triphenyl tetrazolium chloride (TTC) staining and Longa neurologic score were performed to evaluate the outcomes after ischemic stroke. Inflammatory factors expression levels in the serum, ischemic hemisphere brain, and small intestine were detected. Additionally, the morphology change of small intestine was evaluated via analyzing villus height and smooth muscle thickness. Meanwhile, the expression of tight-junction proteins, including Zonula Occludens-1(ZO-1), Occludin and Claudin-1, was detected to evaluate the impact of EA on mucosal permeability in the small intestine. The percentage of Treg cells (CD45 + CD4 + Foxp3 + ) and γδ T cells (CD45 + CD4 − γδ T + ) were measured to assess the effect of EA on T cells. Our data showed that EA could significantly decrease the brain infarction volume and intestine barrier injury of the ischemic stroke rats. At the same time, it effectively suppressed the post-stroke inflammation response of the ischemic brain, small intestine, and peripheral serum. More importantly, EA treatment increased the percentage of Treg cells in the small intestine while reducing the rate of γδ T cells, and ultimately increased the ratio of Treg/ γδ T cells. These results suggested that EA could ameliorate intestinal inflammation damage by regulating the Treg/ γδ T cell polarity shift and improving the intestine barrier integrity post-stroke. It may be one of the mechanisms underlying the anti-ischemic injury effects of acupuncture on stroke.

Preeclampsia (PE) is characterized by new-onset hypertension in association with elevated natural killer (NK) cells and inflammatory cytokines, which are likely culprits for decreased fetal weight during PE pregnancies. As progesterone increases during normal pregnancy, it stimulates progesterone-induced blocking factor (PIBF). PIBF has been shown to decrease inflammation and cytolytic NK cells, both of which are increased during PE. We hypothesized that PIBF reduces inflammation as a mechanism to improve hypertension in the preclinical reduced uterine perfusion pressure (RUPP) rat model of PE. PIBF (2.0 µg/mL) was administered intraperitoneally on gestational day 15 to either RUPP or normal pregnant (NP) rats. On day 18, carotid catheters were inserted. Mean arterial blood pressure (MAP) and samples were collected on day 19. MAP in NP rats (n = 11) was 100 ± 2 mmHg and 105 ± 3 mmHg in NP + PIBF rats (n = 8) and 122 ± 1 mmHg in RUPP rats (n = 10), which improved to 110 ± 2 mmHg in RUPP + PIBF rats (n = 11), P < 0.05. Pup weight was 2.4 ± 0.1 g in NP, 2.5 ± 0.1 g in NP + PIBF, 1.9 ± 0.1 g in RUPP, and improved to 2.1 ± 0.1 g in RUPP + PIBF rats. Circulating and placental cytolytic NK cells, IL-17, and IL-6 were significantly reduced while IL-4 and T helper (TH) 2 cells were significantly increased in RUPP rats after PIBF administration. Importantly, vasoactive pathways preproendothelin-1, nitric oxide, and soluble fms-Like tyrosine Kinase-1 (sFlt-1) were normalized in RUPP + PIBF rats compared with RUPP rats, P < 0.05. Our findings suggest that PIBF normalized IL-4/TH2 cells, which was associated with improved inflammation, fetal growth restriction, and blood pressure in the RUPP rat model of PE.

The present study aimed to investigate the effect of epigallocatechin gallate (EGCG) on airway inflammation in mice with bronchial asthma, and the regulatory mechanism of transforming growth factor (TGF)‑β1 signaling pathway, so as to provide theoretical basis for research and development of a novel drug for clinical treatment. Mouse models of bronchial asthma were established and injected with dexamethasone and EGCG via the caudal vein. 7 days later, bronchoalveolar tissue was collected for hematoxylin and eosin staining. Determination of airway resistance (AWR) and lung function in mice was detected. Serum was separated for cytometric bead array to detect the changes in inflammatory factors. Bronchoalveolar lavage fluid was collected for eosinophil and neutrophil counts. Fresh blood was obtained for flow cytometry to determine the percentages of Th17 and Treg cells. Bronchovesicular tissue was utilized for western blot assay and reverse transcription‑quantitative polymerase chain reaction to determine the proteins and transcription factors in the TGF‑β1 pathway. EGCG 20 mg/kg significantly reduced asthmatic symptoms, lung inflammatory cell infiltration, and the inflammatory factor levels of interleukin (IL)‑2, IL‑6 and tumor necrosis factor (TNF)‑α. In addition, it increased the levels of inflammatory factors, including IL‑10, diminished the percentage of Th17 cells, increased the percentage of Treg cells, and decreased the expression of TGF‑β1 and phosphorylated (p)‑Smad2/3 expression. Following the inhibition of the TGF‑β1 receptor, the anti‑inflammatory effect of EGCG disappeared, and the expression of TGF‑β1 and p‑Smad2/3 increased. EGCG attenuated airway inflammation in asthmatic mice, decreased the percentage of Th17 cells and increased the percentage of Treg cells. The anti‑inflammatory effect of EGCG is achieved via the TGF‑β1 signaling pathway.