Rongbiao Pi

Ethnopharmacological relevance: Huai-Hua-San (HHS), a classical Chinese medicine formula comprising Sophorae Flos (the dried flower/flower bud of Sophora japonica L.) and Gardeniae Fructus (the dried fruit of Gardenia jasminoides Ellis), was recorded in Pu-Ji-Fang (1406) for intestinal bleeding and inflammation—symptoms relevant to colorectal pathology. In modern practice, HHS-containing preparations are used as adjunctive therapy for colorectal cancer (CRC). The pharmacological basis for its application in CRC remains to be clarified.Aim of the study: To evaluate the anti-CRC efficacy and safety of an ethanolic extract of HHS (HHSE) and to elucidate the underlying molecular mechanisms.Materials and methods: HHSE was prepared by ultrasonic extraction with 60% ethanol, followed by enrichment on D101 macroporous resin and chemical analysis using UPLC-QTOF-MS/MS. Anti-CRC activity was assessed in vitro (HCT116, HT-29; normal control: CCD 841 CoN) and in vivo (HT-29 xenograft model). Network pharmacology identified putative targets and pathways, which were examined using immunoblotting, Hsp90α ATPase assays, cycloheximide-chase analyses, and functional modulation with SC79-mediated AKT activation and Hsp90α overexpression.Results: HHSE selectively reduced CRC cell viability, induced apoptosis, and suppressed HT-29 xenograft growth without overt toxicity. Network analyses highlighted PI3K/AKT signaling and the nodes AKT, PI3K, EGFR, and Hsp90α. Consistently, HHSE decreased phosphorylation of AKT (Ser473) and EGFR (Tyr1068), reduced PI3K levels, and lowered the AKT downstream anti-apoptotic proteins Mcl-1 and Bcl-xL. HHSE also reduced both the protein level and ATPase activity of Hsp90α and accelerated the turnover of its client proteins, EGFR and AKT. Activation of AKT with SC79 and overexpression of Hsp90α each attenuated HHSE-induced growth inhibition.Conclusions: HHSE exhibits anti-CRC effects involving AKT suppression and Hsp90α downregulation. These findings support the traditional application of HHS in CRC-related conditions and motivate further development and standardization of HHSE.

It is reported that retinal abnormities are related to Alzheimer’s disease (AD) in patients and animal models. However, it is unclear whether the retinal abnormities appear in the mouse model of sporadic Alzheimer’s disease (sAD) induced by acrolein. We investigated the alterations of retinal function and structure, the levels of β-amyloid (Aβ) and phosphorylated Tau (p-Tau) in the retina, and the changes in the retinal vascular system in this mouse model. We demonstrated that the levels of Aβ and p-Tau were increased in the retinas of mice from the acrolein groups. Subsequently, a decreased amplitudes of b-waves in the scotopic and photopic electroretinogram (ERG), decreased thicknesses of the retinal nerve fiber layer (RNFL) in the retina, and slight retinal venous beading were found in the mice induced by acrolein. We propose that sAD mice induced by acrolein showed abnormalities in the retina, which may provide a valuable reference for the study of the retina in sAD.

The role of dietary fiber in highland barley in lowering blood lipids has been continuously studied in recent years. However, its effects on diabetes and diabetic nephropathy are rarely studied. Considering that highland barley bran is rich in dietary fiber, the effective use of dietary fiber in highland barley bran can not only alleviate the symptoms of diabetes but also improve the local economy. This article aimed to study the effects of highland barley fiber-rich powder (T-fiber) with a high-quality natural dietary fiber ratio (insoluble fiber/soluble fiber=3:1) on the symptoms of hyperglycemia in a diabetic mouse model. Compared with the model groups blood glucose level (30.80mmol/L), glucose tolerance (28.57mmol/L), and glycosylated serum protein (2.43mmol/L), T-fiber presented significant reductions in blood glucose (23.69mmol/L), better glucose tolerance (21.32mmol/L), and glycosylated serum protein (1.78mmol/L) in the diabetic mouse model. Meanwhile, T-fiber effectively alleviated hepatocellular lesions. In addition, T-fiber not only improved kidney function by reducing the 24-hour urine output (8.25ml), urine protein levels (11.51mg), and serum creatinine (13.80μmol/L) but also alleviated renal pathology, including glomerular hypertrophy, mesangial expansion, and fibrosis. The above results proved the ability of T-fiber to reduce blood glucose and alleviate liver and renal function in diabetic mice. Altogether, T-fiber is a capable formula for utilizing highland barley bran dietary fiber, which alleviates diabetes symptoms and endows highland barley with promising value.

Background: Traumatic brain injury, one of the leading causes of death in adults under 40 years of age in the world, is frequently caused by mechanical shock, resulting in diffuse neuronal damage and long-term cognitive dysfunction. Many existing TBI animal models revival with expensive equipment or special room are needed or the processes of operations are complex and not easy to be widely used. Therefore, a simpler TBI model needs to be designed. Methods: Our TBI model is an innovation of the modeling method through air guns shutting rubber bullets. A core facet is the application of our designed rubber bullet impact device. It could focus the hitting power to the fixed site of the brain, thus triggering a mild closed head injury. Moreover, the degree of damage can be adjusted by the times of shots. Results: Our model induced blood-brain barrier leakage and diffused neuronal damage. Besides, it led to an increased level of Tau phosphorylation and resulted in cognitive dysfunction within several weeks post-injury. Conclusion: Our TBI model is not only simple and time-saving but also can simulate mild brain injuries in clinical. It is suitable for exploring pathobiological mechanisms as well as a screening of potential therapies for TBI.

Acrolein, an unsaturated aldehyde, is increased in the brain of Alzheimer's disease (AD) patients and identified as a potential inducer of sporadic AD. Synaptic dysfunction, as a typical pathological change occurring in the early stage of AD, is most closely associated with the severity of dementia. However, there remains a lack of clarity on the mechanisms of acrolein inducing AD‐like pathology and synaptic impairment. In this study, acrolein‐treated primary cultured neurons and mice were applied to investigate the effects of acrolein on cognitive impairment and synaptic dysfunction and their signaling mechanisms. In vitro, ROCK inhibitors, Fasudil, and Y27632, could attenuate the axon ruptures and synaptic impairment caused by acrolein. Meanwhile, RNA‐seq distinct differentially expressed genes in acrolein models and initially linked activated RhoA/Rho‐kinase2 (ROCK2) to acrolein‐induced synaptic dysfunction, which could regulate neuronal cytoskeleton and neurite. The Morris water maze test and in vivo field excitatory postsynaptic potential (fEPSP) were performed to evaluate spatial memory and long‐term potential (LTP), respectively. Acrolein induced cognitive impairment and attenuated LTP. Furthermore, the protein level of Synapsin 1 and postsynaptic density 95 (PSD95) and dendritic spines density were also decreased in acrolein‐exposed mice. These changes were improved by ROCK2 inhibitor Fasudil or in ROCK2^+/− mice. Together, our findings suggest that RhoA/ROCK2 signaling pathway plays a critical role in acrolein‐induced synaptic damage and cognitive dysfunction, suggesting inhibition of ROCK2 should benefit to the early AD.