Saffron Petal, an Edible Byproduct of Saffron, Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting Macrophage Activation and Regulating Gut Microbiota.

Saffron petal (SP) is an agricultural byproduct in the process of the crude drug saffron, accounting for 90% of the dry weight of saffron flowers. To promote the utilization of SP in the food and pharmaceutical industries, its anti-inflammatory activities were evaluated on LPS-activated RAW 264.7 cells and DSS-challenged colitic mice. The results indicated that the SP extract had a notable effect in alleviating the clinical manifestations of colitis, such as reduction in body weight, improvement in disease activity index, mitigation of colon shortening, and alleviation of colon tissue damage. Moreover, SP extract significantly suppressed macrophage infiltration and activation, evidenced by a decrease in colonic F4/80 macrophages and suppression of the transcription and secretion of colonic tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in DSS-challenged colitic mice. In vitro, SP extract also significantly suppressed nitric oxide production, COX-2 and iNOS expressions, and TNF-α and IL-1ß transcription of activated RAW 264.7 cells. Network pharmacology-guided research identified that SP extract significantly downregulated Akt, p38, ERK, and JNK phosphorylation in vivo and in vitro. In parallel, SP extract also effectively corrected microbial dysbiosis by increasing the abundance of Bacteroides acidifaciens, Bacteroides vulgatus, Lactobacillus murinus, and Lactobacillus gasseri. These findings indicate that the effectiveness of SP extract in treating colitis is demonstrated by its ability to reduce macrophage activation, inhibit the PI3K/Akt and MAPK pathways, and regulate gut microbiota, suggesting that SP extract holds great potential as a therapeutic option for colitis.

Picroside III, an Active Ingredient of Picrorhiza scrophulariiflora, Ameliorates Experimental Colitis by Protecting Intestinal Barrier Integrity.

This study aims to explore the protective effects of Picroside III, an active ingredient of Picrorhiza scrophulariiflora, on the intestinal epithelial barrier in tumor necrosis factor-α (TNF-α) induced Caco-2 cells and dextran sulfate sodium (DSS) induced colitis in mice. Results show that Picroside III significantly alleviated clinical signs of colitis including body weight loss, disease activity index increase, colon shortening, and colon tissue damage. It also increased claudin-3, ZO-1 and occludin expressions and decreased claudin-2 expression in the colon tissues of mice with colitis. In vitro, Picroside III also significantly promoted wound healing, decreased the permeability of cell monolayer, upregulated the expressions of claudin-3, ZO-1 and occludin and downregulated the expression of claudin-2 in TNF-α treated Caco-2 cells. Mechanism studies show that Picroside III significantly promoted AMP-activated protein kinase (AMPK) phosphorylation in vitro and in vivo, and blockade with AMPK could significantly attenuate the upregulation of Picroside III in ZO-1 and occludin expressions and the downregulation of claudin-2 expression in TNF-α treated Caco-2 cells. In conclusion, this study demonstrates that Picroside III attenuated DSS-induced colitis by promoting colonic mucosal wound healing and epithelial barrier function recovery via the activation of AMPK.

Network Pharmacology Study of Bioactive Components and Molecular Mechanisms of the Glycoside Fraction from Picrorhiza scrophulariiflora Against Experimental Colitis.

Purpose: To explore the potential mechanism of glycosidic fraction of Picrorhiza scrophulariiflora Pennell (GPS) extract for the treatment of colitis using UPLC-QTOF-MS analysis, network pharmacology and experimental research. Methods: The active components of GPS extract were identified by UPLC-QTOF-MS analysis and extracted their targets from the databases, which was used for network pharmacology analysis. Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis was performed to discover potential therapeutic mechanisms, and the network pharmacology results were then validated by in vivo and in vitro experiments. Results: The results showed that GPS extract significantly alleviated the clinical signs of colitis, including body weight, disease activity index, colon shortening, and colon tissue damage, and inhibited the transcription and production of colonic IL-1ß and IL-6 in DSS-induced colitis mice. In vitro, GPS extract also significantly suppressed nitric oxide (NO) production, iNOS expression, IL-1ß and IL-6 transcription of LPS-activated RAW 264.7 cells. Network pharmacology integrated with experimental validation identified that GPS extract significantly suppressed Akt, p38, ERK, and JNK phosphorylation in vivo and in vitro, and luteolin, apocynin, caffeic acid, caffeic acid methyl ester, luteoloside, picroside II, aucubin, cinnamic acid, vanillic acid, and sweroside were the main components responsible for the anti-inflammatory effect of GPS. These findings demonstrate that the potential anti-inflammatory effect of GPS extract against colitis is achieved through suppressing PI3K/Akt and MAPK pathways, and that the abovementioned active components mainly exerted its anti-inflammatory effect. Conclusion: The therapeutic effect of GPS extract on colitis is related to PI3K/Akt and MAPK pathways, which is a promising remedy for colitis therapy.

Fuc-S-A New Ultrasonic Degraded Sulfated α-l-Fucooligosaccharide-Alleviates DSS-Inflicted Colitis through Reshaping Gut Microbiota and Modulating Host-Microbe Tryptophan Metabolism.

SCOPE: The dysbiosis of intestinal microecology plays an important pathogenic role in the development of inflammatory bowel disease. METHODS AND RESULTS: A polysaccharide named Fuc-S, with a molecular weight of 156 kDa, was prepared by the ultrasonic degradation of fucoidan. Monosaccharide composition, FTIR, methylation, and NMR spectral analysis indicated that Fuc-S may have a backbone consisting of →3)-α-L-Fucp-(1→, →4)-α-L-Fucp-(1→ and →3, 4)-α-D-Glcp-(1→. Moreover, male C57BL/6 mice were fed three cycles of 1.8% dextran sulfate sodium (DSS) for 5 days and then water for 7 days to induce colitis. The longitudinal microbiome alterations were evaluated using 16S amplicon sequencing. In vivo assays showed that Fuc-S significantly improved clinical manifestations, colon shortening, colon injury, and colonic inflammatory cell infiltration associated with DSS-induced chronic colitis in mice. Further studies revealed that these beneficial effects were associated with the inhibition of Akt, p-38, ERK, and JNK phosphorylation in the colon tissues, regulating the structure and abundance of the gut microbiota, and modulating the host-microbe tryptophan metabolism of the mice with chronic colitis. CONCLUSION: Our data confirmed the presence of glucose in the backbone of fucoidan and provided useful information that Fuc-S can be applied as an effective functional food and pharmaceutical candidate for IBD treatment.

Berberine Suppresses Colonic Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis Through Inhibition of Cytosolic Phospholipase A2 Activity.

Ulcerative colitis (UC) causes chronic inflammation and damage to the colonic mucosal layer. Recent studies have reported significant changes in phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in UC patients and oral administration of PC has considerable therapeutic effects against UC, suggesting the metabolism of phosphatidylcholine may be involved in the UC development. Our previous work has demonstrated that berberine effectively suppresses inflammation and protects colonic mucosa injury in DSS-induced colitic mice. However, whether the therapeutic effects of berberine are attributed to its action on the PC metabolism remains unknown. In the present study, we have shown that berberine significantly reduces the lysophosphatidylcholine (LPC) levels in the sera of DSS-induced experimental colitis mice and LPS-stimulated macrophage RAW 264.7 cells. The cytosolic phospholipase A2a (PLA2G4A), an enzyme for hydrolyzing PC to LPC, was found to be up-regulated in the colon tissue of experimental colitis mice and inflamed macrophage RAW 264.7 cells. We then demonstrated berberine inhibits the phosphorylation of cytosolic phospholipase A2a (PLA2G4A) in the colon tissue of experimental colitis mice and inflamed macrophage RAW 264.7 cells. Subsequently, we revealed berberine suppressed the expression of pro-inflammatory factors including TNF-alpha and IL-6 through regulating PLA2G4A dysfunction in macrophage RAW 264.7 cells. Mechanistically, we found that berberine directly binds to PLA2G4A and inhibits MAPK/JNK signaling pathway to inhibit PLA2G4A activity in inflammatory status. Therefore, we concluded that berberine inhibits colonic PLA2G4A activity to ameliorate colonic inflammation in experimental colitic mice, suggesting modulation of the PC metabolism via PLA2G4A might be beneficial for establishing new therapies strategy for UC.

Distribution patterns of the contents of five biologically activate ingredients in the root of Scutellaria baicalensis.

As an important herbaceous plant, Scutellaria baicalensis Georgi (Chinese skullcap) is geographically widespread and commonly used throughout the world. In the Chinese medicine market, S. baicalensis has been divided into two primary types, "Ku Qin" (WXR) and "Tiao Qin" (TST). Moreover, TST is also divided into different grades according to the diameter of roots. To explore the distribution patterns of the contents of five biologically activate ingredients (FBAI), we used six-year-old cultivated S. baicalensis and analyzed its growth characteristics as well as the quality difference among different types and diameters in roots. Throughout the entire root, we discovered that contents of the FBAI all initially increased and subsequently decreased from the top to the bottom of the roots. The baicalin content of WXR was less than that of TST. On the contrary, the contents of baicalein, wogonin, and oroxylin A in WXR were up to about two times higher than that in TST. We also found that the 0 to 40 cm part of the S. baicalensis root possessed about 87% of the root biomass and about 92% of the contents of the active ingredients.

[Study on difference of functional components content of different Rheum tanguticum variation type].

Rheum tanguticum from the same area was divided into 8 types of variation according to the plant morphology, content differences of free anthraquinones, combined anthraquinones, double anthrone were studied. The results showed that the functional components of different variation types were significantly different. The average content of free anthraquinone combined anthraquinone was 2.10-6.71 and 15.43-22.04 mg•g⁻¹, respectively. The average content of sennoside A plus sennoside B was 32.88-42.36 mg•g⁻¹. There were significant differences among the difference of 10 kinds of active components, except for sennoside B and physcion glycoside. Interred with the content and proportion of functional components, type B and type E might be potential special medicinal germplasm for diarrhea attack product, type G and type H might be a potential special medicinal germplasm for clearing heat and detoxifing, type C and type F might be potential special medicinal germplasm for activating blood circulation to dissipate blood stasis, type A and type D might be potential special medicinal germplasm with anastaltic funtion. The conclusion laid the foundation for the directional cultivation of fine varieties of special purpose of rhubarb.

[Therapeutic effect of sirolimus against chronic allograft nephropathy in kidney transplant recipients].

OBJECTIVE: To investigate the efficacy and safety of sirolimus in management of chronic allograft nephropathy (CAN). METHODS: A retrospective study was conducted involving 31 CAN patients followed up since March 2002, who experienced a change from a calcineurin inhibitor (CNI)-based regimen to a SRL-based regimen. Serum creatinine (Cr) in these patients was compared before and after the regimen change, and the adverse events associated with SRL were analyzed. RESULTS: Till March 2007 when the study closed, 15 patients reached the primary endpoint for resuming dialysis, 8 had improved and 8 had stable renal function. In patients with high Cr(0)(> or =3 mg/L, n=12), 9 resumed dialysis and 2 had improved renal function, but one of the patients with renal improvement eventually died due to infection; in the patients with low Cr(0)(<3 mg/L, n=19), 5 resumed dialysis, 8 had stable renal function and 6 had improved renal function, showing significant difference between the 2 groups (P=0.003). Altogether 14 patients reached the secondary endpoint for ceasing SRL for severe infection (5 patients, of whom 4 resumed dialysis and 1 died of infection) or adverse events associated with SRL (9 patients, of whom 4 resumed dialysis, 2 had stable and 3 had improved renal function). Hyperlipidemia (51.6%), leukocytopenia (41.9%), mouth ulcer (29.0%) and liver function lesion (16.1%) were the commonest adverse events in these patients, and totalling 13 severe adverse events were recorded, including 2 fatal cerebral hemorrhage, 3 fatal infection episodes, and 8 pulmonary and urinary infections that require hospitalization. CONCLUSION: Conversion from a CNI-based to SRL-based regimen can be effective for some CAN cases, especially for those with Cr(0) below 3 mg/L. Attention must be given to adverse events like hyperlipidemia and leukocytopenia, as well as the related cerebral vascular accidents and infections.

[Characteristics of neoplasm occurrence of renal allograft recipients and their prognosis].

BACKGROUND & OBJECTIVE: Renal allograft recipients are more likely to develop neoplasm than general population because of long-term immunosuppressive treatment and concurrent infections. This study was designed to analyze the clinical features of neoplasm occurrence of renal allograft recipients, and the effect of radical surgery (RS) on their prognosis. METHODS: Records of 2 160 renal allograft recipients treated in our center from Oct. 1987 to Apr. 2003 were retrospectively studied. The time to neoplasm development, pathologic type of tumor, patients' survival time were analyzed to explore the clinical features of neoplasm developing after kidney transplantation. Recipients developed neoplasms were divided into RS group and non-RS group according to their treatment pattern. The effect of RS on patients' survival was estimated. RESULTS: A total of 33 patients developed neoplasms after transplantation. Among them,11(33.3%) developed neoplasms in digestive system. The median survival time of RS group (10 patients) was 41.5 months, that of non-RS group (23 patients) was 6.0 months. The 20-month survival rate of RS group was 70.0%, while that of non-RS group was 13.0%. CONCLUSIONS: Renal allograft recipients are more likely to develop neoplasm than general population. Moreover, their main malignancies are liver cancer, skin cancer, lymphoma and thyroid carcinoma, which differ from those observed in general population. Early diagnosis and treatment, especially feasible RS, will improve short-term outcome, while long-term therapeutic effect needs to be further observed.