Casearia sylvestris var. lingua (Càmbess.) Eichler leaves aqueous extract improves colon inflammation through mucogenic, antioxidant and anti-inflammatory actions in TNBS- induced IBD rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris var. lingua (Cambess.) Eichler, a member of the Salicaceae family, holds a prominent place in traditional medicine across various cultures due to its versatile therapeutic properties. Historically, indigenous communities have utilized different parts of the plant, including leaves, bark, and roots, to address a wide array of health conditions. Traditional uses of C. sylvestris var. lingua encompasses the treatment of gastrointestinal disorders, respiratory infections, wound healing, inflammation, and stomach ulcers. Pharmacological studies have demonstrated the plant's antimicrobial, anti-inflammatory, antioxidant, analgesic, gastroprotective, and immunomodulatory effects. This signifies the first scientific validation report for C. sylvestris var. lingua regarding its effectiveness against ulcerative colitis. The report aims to affirm the traditional use of this plant through pre-clinical experiments. AIM OF THE RESEARCH: This work uses an aqueous extract from C. sylvestris var. lingua leaves (AECs) to evaluate the acute anti-ulcerative colitis efficacy in rat and HT-29 (human colorectal cancer cell line) models. METHODS: To determine the secondary metabolites of AECs, liquid chromatography with a diode array detector (LC-DAD) study was carried out. 2,4,6-trinitrobenzenesulfonic acid (TNBS, 30 mg/0.25 mL EtOH 30% v/v) was used as an enema to cause acute colitis. Three days were spent giving the C. sylvestris var. lingua extract orally by gavage at dosages of 3, 30, and 300 mg/kg. The same route was used to deliver distilled water to the vehicle and naïve groups. After the animals were sacrificed on the fourth day, intestinal tissues were taken for histological examination and evaluation of biochemical tests such as those measuring superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA), nitrite/nitrate, myeloperoxidase (MPO) activity. Additionally, interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10), were conducted on the intestinal tissues. Additionally, an MTT assay was used to evaluate the effect of AECs on the viability of HT-29 cells. Additionally, a molecular docking study was carried out to compare some potential target proteins with identified chemicals found in AECs. RESULTS: LC-DAD analysis identified five compounds (caffeic acid, ellagic acid, ferulic acid, gallic acid, and quercetin) in AECs. Pre-administration of AECs (3; 30; 300 mg/kg) and mesalazine (500 mg/kg) reduced macroscopic scores (55%, 47%, 45%, and 52%, p < 0.001) and ulcerated areas (70.3%, 70.5%, 57%, and 56%, p < 0.001), respectively. It also increased SOD, GSH, and CAT activities (p < 0.01), while decreasing MDA (p < 0.001), nitrite/nitrate (p < 0.05), and MPO (p < 0.001) activities compared to the colitis group. Concerning inflammatory markers, significant modulations were observed: AECs (3, 30, and 300 mg/kg) lowered levels of IL-1ß and TNF-α (p < 0.001) and increased IL-10 levels (p < 0.001) compared to the colitis groups. The viability of HT-29 cells was suppressed by AECs with an IC50 of 195.90 ± 0.01 µg/mL (48 h). During the molecular docking analysis, quercetin, gallic acid, ferulic acid, caffeic acid, and ellagic acid demonstrated consistent binding affinities, forming stable interactions with the 3w3l (TLR8) and the 3ds6 (MAPK14) complexes. CONCLUSION: These results imply that the intestinal mucogenic, anti-inflammatory, and antioxidant properties of the C. sylvestris var. lingua leaf extract may be involved in its therapeutic actions for ulcerative colitis. The results of the in silico study point to the possibility of quercetin and ellagic acid interacting with P38 and TLR8, respectively, in a beneficial way.

Mesenchymal Stromal Cell Therapy Reverses Detrusor Hypoactivity in a Chronic Kidney Patient.

Detrusor hypoactivity (DH) is characterized by low detrusor pressure or a short contraction associated with low urinary flow. This condition can progress to chronic renal failure (CRF) and result in the need for dialysis. The present case report demonstrates that a patient diagnosed with DH and CRF who received two transplants with 2 × 106 autologous mesenchymal stromal cells at an interval of 30 days recovered the contractile strength of the bladder and normalized his renal function. The patient had a score of 19 on the ICIQ-SF before cell therapy, and that score was reduced to 1 after transplantation. These results demonstrate that there was an improvement in his voiding function, urinary stream and urine volume as evaluated by urofluxometry. In addition, a urodynamic study carried out after treatment showed an increase in the maximum flow from 2 mL/s to 23 mL/s, the detrusor pressure in the maximum flow from 21 cm H2O to 46 cm H2O and a BCI that went from 31 to 161, characterizing good detrusor contraction. Thus, in the present case, the transplantation of autologous mesenchymal stromal cells proved to be a viable therapeutic option to allow the patient to recover the contractile strength of the bladder, and reversed the CRF.

Autologous adipose-derived mesenchymal stem cell therapy reverses detrusor underactivity: open clinical trial.

BACKGROUND: Detrusor underactivity is a disease that can cause chronic urinary tract infection, urinary tract infection, urinary retention and kidney failure and has no effective treatment in traditional medicine. The present research evaluated the effects of cell therapy with adipose tissue-derived stem cells on the treatment of detrusor underactivity in men. METHODS: Nine male patients diagnosed with a clinical and urodynamic diagnosis of detrusor underactivity were evaluated and underwent two transplants via cystourethroscopy, with 2 × 106 cells/transplant, performed by intravesical injection at five points on the bladder body above the vesical trigone. RESULTS: Cell therapy increased the maximum flow from 7.22 ± 1.58 to 13.56 ± 1.17, increased the mean flow from 3.44 ± 0.74 to 5.89 ± 0.45, increased the urinated volume from 183.67 ± 49.28 to 304.78 ± 40.42 and reduced the residual volume in the uroflowmetry exam from 420.00 ± 191.41 to 118.33 ± 85.51; all of these changes were significant (p < 0.05). There were also significant increases (p < 0.05) in maximum flow (from 7.78 ± 0.76 to 11.56 ± 1.67), maximum detrusor pressure (from 20.22 ± 8.29 to 41.56 ± 5.75), urinary volume (from 244 ± 27.6 to 418.89 ± 32.73) and bladder contractility index (from 44.33 ± 4.85 to 100.56 ± 8.89) in the pressure flow study. Scores on the International Consultation on Incontinence Questionnaire decreased from 11.44 ± 1.43 to 3.78 ± 0.78 after cell therapy, which indicates an improvement in quality of life and a return to daily activities. No complications were observed in the 6-month follow-up after cell therapy. Before treatment, all patients performed approximately five intermittent clean catheterizations daily. After cell therapy, 7/9 patients (77.78%) did not need catheterizations, and the number of catheterizations for 2/9 patients (22.28%) was reduced to two catheterizations/day. CONCLUSIONS: The results indicate that stem cell therapy led to improvements in voiding function. Cell therapy with adipose tissue-derived stem cells is safe and should be considered a new therapeutic option for the treatment of detrusor underactivity. Trial registration ISRCTN, ISRCTN23909398; Registered 15 March 2021-Retrospectively registered, https://doi.org/10.1186/ISRCTN23909398.

The Ethanolic Extract of Piper glabratum Kunth Is Teratogenic and Interferes with the Ossification Process of Swiss Mice Fetuses.

Piper glabratum Kunth is a plant traditionally used to treat pain and inflammation in the Mato Grosso do Sul, Brazil. Even pregnant women consume this plant. Toxicology studies of the ethanolic extract from the leaves of P. glabratum (EEPg) could establish the safety of popular use of P. glabratrum. Thus, the effects of the ethanolic extract of leaves of P. glabratum (EEPg) on the reproductive performance and embryofetal development of Swiss mice were evaluated. Pregnant female mice were treated with 100, 1000 and 2000 mg/kg throughout the gestational period by gavage (p.o). The control group received the EEPg vehicle (Tween 80-1%) in the proportion of 0.1 mL/10 g (p.o.). The results demonstrated that EEPg has low maternal toxic potential and does not alter the reproductive performance of females. However, it altered embryofetal development and caused fetal weight reduction (increasing the frequency of small-for-gestational-age fetuses) at the two highest doses. In addition, it interfered with placental weight, placental index and placental efficiency. The frequency of visceral malformations increased by 2.8 times for the lowest dose of EEPg, and skeletal malformations increased by 2.48, 1.89 and 2.11 times for doses of 100, 1000 and 2000 mg/kg of EEPg, respectively. It is noteworthy that 100% of the offspring treated with EEPg showed changes in the ossification process. Thus, it is considered that the EEPg has low maternal toxic potential; it does not alter the reproductive performance of females. However, it is teratogenic and interferes, mainly, in the ossification process, and therefore its use is contraindicated in the gestational period.

Aqueous extract from leaves of Doliocarpus dentatus (Aubl.) Standl. relieves pain without genotoxicity activity.

ETHNOPHARMACOLOGICAL RELEVANCE: In the State of Mato Grosso do Sul, the watery sap of Doliocarpus dentatus is used to alleviate thirst, and the leaves of this species are used to relieve pain and swelling associated with inflammatory processes. AIM OF THE STUDY: This study aimed to analyze the compounds of the leaves from the aqueous extract of D. dentatus (EADd) and evaluate its toxicogenetic and pain relief effects in animal models. MATERIALS AND METHODS: Compounds were identified in EADd by UHPLC-HRMS (Ultra high-performance liquid chromatography coupled to high resolution mass spectrometry). The oral dose of 17 mg/kg EADd, calculated according to ethnopharmacological uses, and doses between 30 and 300 mg/kg were used to test Swiss mice in formalin- and acetic acid-induced models of pain and behavior. EADd (100-2000 mg/kg) was assayed in mice by comet, micronucleus, and phagocytosis tests and by peripheral leukocyte counts. RESULTS: Phenolic compounds and flavonoids as well as trigonelline and isoquercetin were identified in EADd. All oral doses of EADd exhibited antinociceptive activity, as indicated by a decrease in pain in both phases, a decrease in cold hypersensitivity induced by formalin, and a decrease in abdominal contortions induced by acetic acid. EADd did not alter the exploratory, motor or motivational activities of the animals. The comet and micronucleus tests indicated that EADd was not genotoxic and did not change the phagocytic activity or peripheral leukocyte count. CONCLUSIONS: These results demonstrate that EADd could act as an antinociceptive agent that does not present genotoxicity. This study should contribute to justifying, in part, the popular use of D. dentatus in pain management, ensuring its safe use.