The anti-colorectal cancer effect and metabolites of Agrimonia pilosa Ledeb.

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia pilosa Ledeb. (Rosaceae, A. pilosa) has been used in traditional medicine in China, Japan, Korea, and other Asian countries for treatment of acute and chronic enteritis and diarrhea. Secondary metabolites have been isolated and tested for biological activities. It remains unclear in terms of its potential components of anti-colorectal cancer properties. AIM OF THE STUDY: The study aimed to how extracts from A. pilosa and their components influenced tumor microenvironment and the colorectal tumor growth in vivo on AOM/DSS induced colorectal cancer mice, the metabolites of A. pilosa was also been studied. MATERIALS AND METHODS: Different methods have been used to extract different parts of A. pilosa. And the anti-proliferation effect of these extracts on colon cancer cells have been tested. The components of A. pilosa and its metabolites in vivo were analyzed by UPLC-QTOF-MS/MS. The anti-colorectal cancer (CRC) effects of A. pilosa and its components in vivo were studied on AOM/DSS induced CRC mice. The effects of constituents of A. pilosa on the composition of immune cells in tumor microenvironment (TME) were analyzed by flow cytometry. 16 S rDNA technology was used to analyze the effect of administration on the composition of intestinal microflora. Pathological section staining was used to compare the morphological changes and molecular expression of intestinal tissue in different groups. RESULTS: The constituent exists in root of A. pilosa showed the strongest anti-proliferation ability on colon cancer cells in vitro. The extract from the root of A. pilosa could attenuate the occurrence of colorectal tumors induced by AOM/DSS in a concentration-dependent manner. Administration of the extract from the root of A. pilosa could affect the proportion of γδT cells, tumor associated macrophages and myeloid derived suppressor cells in TME, increasing the proportion of anti-tumor immune cells and decrease the immunosuppressive cells in the TME to promote the anti-tumor immune response. The administration of the extract adjusted the composition of gut microbiota and its components Agrimoniin and Agrimonolide-6-o-glucoside showed the strongest anti-CRC effect in vivo with adjusting the gut microbiota differently. CONCLUSIONS: The extract from root of A. pilosa showed anti-colorectal cancer effects in vivo and in vitro, affecting the composition of gut microbiota and the anti-tumor immune response. Within all components of A. pilosa, Agrimoniin and Agrimonolide-6-o-glucoside showed remarkable anti-CRC efficiency in vivo and in vitro. Besides, the metabolites of extract from root of A. pilosa in gastrointestinal tract mainly composed of two parts: Agrimonolide-related metabolites and Urolithins. The extract from root of A. pilosa could contribute to potential drugs for assisting clinical anti-colon cancer therapy.

Co-assembled Supramolecular Hydrogel of Salvianolic Acid B and a Phosphopeptide for Enhanced Wound Healing.

Supramolecular natural product gels (NPGs) have emerged as promising biomaterials for scalable and adjustable drug delivery systems. These gels possess biocompatibility, biodegradability, and the ability to mimic the extracellular matrix. Salvianolic acid B (SAB), derived from Salvia miltiorrhiza, a Chinese medicinal plant, exhibits various beneficial properties such as antioxidant, antifibrotic, and angiogenic effects. In our research, we serendipitously discovered that the co-assembly of SAB and a soluble phosphopeptide results in the formation of a robust and adhesive hydrogel termed 1&SAB hydrogel. This hydrogel effectively prolongs the retention time of the therapeutic agents on the skin's wound surface, thereby promoting wound healing. The hydrogel demonstrates antioxidant effects, enhances cell migration, accelerates angiogenesis, and inhibits scar hyperplasia. This innovative gel material offers a simple and efficient approach to managing skin wounds and holds promise for application in complex wound-healing treatments.

Volatile Oil of Platycladus Orientalis (L.) Franco Leaves Exerts Strong Anti-inflammatory Effects via Inhibiting the IκB/NF-κB Pathway.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1ß and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

Alloreactive cytotoxic T lymphocyte immunotherapy treatment of a patient with metastatic prostate cancer: A case report.

RATIONALE: Cytotoxic T lymphocyte (CTL) immunotherapy is an autologous cellular immune therapy that has been approved for treating patients with malignant tumors. However, there is still limited information regarding the impact of CTL on metastatic prostate cancer (PC) patients with bone metastatic lesions. PATIENT CONCERNS: An 82-year-old male patient complained of interrupted urination, urination pain, and significant dysuria on November 24, 2014. Transurethral resection of the prostate (TURP) and postoperative pathological examination showed prostatic adenocarcinoma, and a SPECT/CT scan demonstrated multiple bone metastases. In addition, prostate specific antigen (PSA) and free PSA (FPSA) levels were 54.54 µg/mL and 2.63 µg/mL, respectively, at the beginning of treatment. DIAGNOSES: The man was diagnosed with prostatic adenocarcinoma and multiple bone metastases. INTERVENTIONS: The patient received 30 cycles of alloreactive CTL (ACTL) immunotherapy regularly. OUTCOMES: Over the course of the 2-year treatment, the PC patient exhibited diminished bone metastasis accompanied by a marked reduction of serum PSA and FPSA from 54.54 and 2.63 µg/ml to 0.003 and <0.006 µg/ml, respectively. LESSONS: Our clinical observations demonstrate that CTL immunotherapy is a viable treatment option for PC patients, particularly those with bone metastatic lesions and high serum levels of PSA and FPSA.

De novo chemoattractants form supramolecular hydrogels for immunomodulating neutrophils in vivo.

Most immunomodulatory materials (e.g., vaccine adjuvants such as alum) modulate adaptive immunity, and yet little effort has focused on developing materials to regulate innate immunity, which get mentioned only when inflammation affects the biocompatibility of biomaterials. Traditionally considered as short-lived effector cells from innate immunity primarily for the clearance of invading microorganisms without specificity, neutrophils exhibit a key role in launching and shaping the immune response. Here we show that the incorporation of unnatural amino acids into a well-known chemoattractant-N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-offers a facile approach to create a de novo, multifunctional chemoattractant that self-assembles to form supramolecular nanofibrils and hydrogels. This de novo chemoattractant not only exhibits preserved cross-species chemoattractant activity to human and murine neutrophils, but also effectively resists proteolysis. Thus, its hydrogel, in vivo, releases the chemoattractant and attracts neutrophils to the desired location in a sustainable manner. As a novel and general approach to generate a new class of biomaterials for modulating innate immunity, this work offers a prolonged acute inflammation model for developing various new applications.