Albuca Bracteata Polysaccharides Attenuate AOM/DSS Induced Colon Tumorigenesis via Regulating Oxidative Stress, Inflammation and Gut Microbiota in Mice

Ding

Oxidative Medicine and Cellular Longevity

et al. 2022

Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An in vitro study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress in vitro. In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.

Section: Discussionmentioning

confidence: 99%

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice

Ding

Oxidative Medicine and Cellular Longevity

et al. 2022

“…Furthermore, a decrease in the Ruminococcaceae family, Oscillospira and Lachnospira genus, species that are related to inflammatory processes [ 21 , 22 , 37 , 57 , 58 , 59 ], was also observed at the finasteride withdrawal [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, whether finasteride treatment may affect steroid levels in the male colon is still unknown. Additionally, the change in the gut microbiota composition previously observed [ 8 ] seems to suggest an inflammatory microenvironment with putative consequences on gut physiology [ 21 , 22 ]. In this context, it is also important to highlight that serotonin, which plays a crucial role in the regulation of several physiological functions, such as motility, secretion and visceral sensitivity [ 23 ], is also related to inflammatory responses in the gut [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Gut Inflammation Induced by Finasteride Withdrawal: Therapeutic Effect of Allopregnanolone in Adult Male Rats

et al. 2022

The treatment with finasteride (i.e., an inhibitor of 5α-reductase) may be associated with different side effects (i.e., depression, anxiety, cognitive impairment and sexual dysfunction) inducing the so-called post finasteride syndrome (PFS). Moreover, previous observations in PFS patients and an experimental model showed alterations in gut microbiota populations, suggesting an inflammatory environment. To confirm this hypothesis, we have explored the effect of chronic treatment with finasteride (i.e., for 20 days) and its withdrawal (i.e., for 1 month) on the levels of steroids, neurotransmitters, pro-inflammatory cytokines and gut permeability markers in the colon of adult male rat. The obtained data demonstrate that the levels of allopregnanolone (ALLO) decreased after finasteride treatment and after its withdrawal. Following the drug suspension, the decrease in ALLO levels correlates with an increase in IL-1β and TNF-α, serotonin and a decrease in dopamine. Importantly, ALLO treatment is able to counteract some of these alterations. The relation between ALLO and GABA-A receptors and/or pregnenolone (ALLO precursor) could be crucial in their mode of action. These observations provide an important background to explore further the protective effect of ALLO in the PFS experimental model and the possibility of its translation into clinical therapy.

“…The polysaccharides extracted from Albuca bracteata (ABPs) were homogeneous polysaccharides with glucose and mannose as the main monosaccharides. ABP treatment could increase the beneficial bacteria in the intestine (for example, g_ Oscillospira ) and total fecal short-chain fatty acid (SCFA) levels in colorectal cancer (CRC) mice . SCFAs are the main end products produced by the fermentation of dietary fiber in the intestines by the intestinal flora .…”

Section: Polysaccharides and Cancersmentioning

confidence: 99%

“…ABP treatment could increase the beneficial bacteria in the intestine (for example, g_Oscillospira) and total fecal short-chain fatty acid (SCFA) levels in colorectal cancer (CRC) mice. 65 SCFAs are the main end products produced by the fermentation of dietary fiber in the intestines by the intestinal flora. 66 The increase of total fecal SCFA concentration represents the increase of dietary polysaccharide decomposition by bacteria in the gut, which will promote the absorption of polysaccharide energy in the body and play a role in preventing colon cancer.…”

Section: ■ Polysaccharides and Cancersmentioning

confidence: 99%

Targeting mTOR Signaling by Dietary Polysaccharides in Cancer Prevention: Advances and Challenges

Guo

et al. 2022

J. Agric. Food Chem.

Cancer is the most serious problem for public health. Traditional treatments often come with unavoidable side effects. Therefore, the therapeutic effects of natural products with wide sources and low toxicity are attracting more and more attention. Polysaccharides have been shown to have cancer-fighting potential, but the molecular mechanisms remain unclear. The mammalian target of rapamycin (mTOR) pathway has become an attractive target of antitumor therapy research in recent years. The regulation of mTOR pathway not only affects cell proliferation and growth but also has an important effect in tumor metabolism. Recent studies indicate that dietary polysaccharides play a vital role in cancer prevention and treatment by regulating mTOR pathway. Here, the progress in targeting mTOR signaling by dietary polysaccharides in cancer prevention and their molecular mechanisms are systemically summarized. It will promote the understanding of the anticancer effects of polysaccharides and provide reference to investigators of this cutting edge field.