A triterpenoid (corosolic acid) ameliorated AOM-mediated aberrant crypt foci in rats: modulation of Bax/PCNA, antioxidant and inflammatory mechanisms.

Corosolic acid (CA) is a well-known natural pentacyclic triterpene found in numerous therapeutic plants that can exhibit many bioactivities including anti-inflammatory and anti-tumor actions. The current investigation explores the chemoprotective roles of CA against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty Sprague Dawley rats were grouped in 5 cages; Group A, normal control rats inoculated subcutaneously (sc) with two doses of normal saline and fed orally on 10% tween 20; Groups B-E received two doses (sc) of azoxymethane in two weeks and treated with either 10% tween 20 (group B) or two intraperitoneal injections of 35 mg/kg 5-fluorouracil each week for one month (group C), while group D and E treated with 30 and 60 mg/kg, respectively, for 2 months. The toxicity results showed lack of any behavioral abnormalities or mortality in rats ingested with up-to 500 mg/kg of CA. The present AOM induction caused a significant initiation of ACF characterized by an increased number, larger in size, and well-matured tissue clusters in cancer controls. AOM inoculation created a bizarrely elongated nucleus, and strained cells, and significantly lowered the submucosal glands in colon tissues of cancer controls compared to 5-FU or CA-treated rats. CA treatment led to significant suppression of ACF incidence, which could be mediated by its modulatory effects on the immunohistochemical proteins (pro-apoptotic (Bax) and reduced PCNA protein expressions in colon tissues). Moreover, CA-treated rats had improved oxidative stress-mediated cytotoxicity indicated by increased endogenous antioxidants (SOD and CAT) and reduced lipid peroxidation indicators (MDA). In addition, CA ingestion (30 and 60 mg/kg) suppressed the inflammatory cascades, indicated by decreased serum TNF-α and IL-6 cytokines and increased anti-inflammatory (IL-10) cytokines consequently preventing further tumor development. CA treatment maintained liver and kidney functions in rats exposed to AOM cytotoxicity. CA could be a viable alternative for the treatment of oxidative-related human disorders including ACF.

A bitter flavonoid gum from Dorema aucheri accelerate wound healing in rats: Involvement of Bax/HSP 70 and hydroxyprolin mechanisms.

BACKGROUND: Dorema aucheri gum (DAG) is a bitter flavonoid gum widely used for numerous medicinal purposes including wound recovery. The present work investigates the acute toxicity and wound-healing effects of DAG in excisional skin injury in rats. MATERIALS AND METHODS: Sprague Dawley rats (24) were clustered into four groups, each rat had a full-thickness excisional dorsal neck injury (2.00 cm) and addressed with 0.2 mL of the following treatments for 15 days: Group A (vehicle), rats addressed with normal saline; Group B, rats received intrasite gel; C and D, rats addressed with 250 and 500 mg/kg of DAG, respectively. RESULTS: The results revealed the absence of any toxic signs in rats who received oral dosages of 2 and 5 g/kg of DAG. Wound healing was significantly accelerated following DAG treatments indicated by smaller open areas and higher wound contraction percentages compared to vehicle rats. Histological evaluation revealed higher fibroblast formation, collagen deposition, and noticeably lower inflammatory cell infiltration in granulated skin tissues of DAG-addressed rats compared to vehicle rats. DAG treatment caused significant modulation of immunohistochemical proteins (decreased Bax and increased HSP 70) and inflammatory mediators (reduced TNF-α, IL-6, and magnified IL-10), which were significantly varied compared to vehicle rats. Moreover, topical DAG treatment led to significant upregulation of the hydroxyproline (HDX) (collagen) and antioxidant content. At the same time, decreased the lipid peroxidation (MDA) levels in healed tissues obtained from DAG-treated rats. CONCLUSION: The present wound contraction by DAG might be linked with the modulatory effect of its phytochemicals (polysaccharides, flavonoids, and phenolic) on the cellular mechanisms, which justify their folkloric use and provokes further investigation as therapeutic drug additives for wound contraction.

Cumin (Cuminum cyminum L.) seeds accelerates wound healing in rats: Possible molecular mechanisms.

Wound healing is a complex, intricate, and dynamic process that requires effective therapeutic management. The current study evaluates the wound healing potentials of methanolic extract of Cuminum cyminum L. seeds (CCS) in rats. Sprague Dawley (24) rats were distributed into four cages, wounds produced on the back of the neck, and received two daily topical treatments for 14 days: A, rats received normal saline; B, wounded rats treated with intrasite gel; C and D, rats received 0.2 mL of 250 and 500 mg/kg of CCS, respectively. After that, wound area and closure percentage were evaluated, and wound tissues were dissected for histopathological, immunohistochemical, and biochemical examinations. Acute toxicity trials of methanolic extract of CCS showed the absence of any physiological changes or mortality in rats. CCS application caused a significant reduction in wound size and a statistically elevated percentage of wound contraction than those of vehicle rats. CCS treatment caused significant up-regulation of collagen fiber, fibroblasts, and fewer inflammatory cells (inflammation) in granulation tissues. TGF-ß1 (angiogenetic factor) was significantly more expressed in CCS-treated rats in comparison to normal saline-treated rats; therefore, more fibroblasts transformed into myofibroblasts (angiogenesis). CCS-treated rats showed remarkable antioxidant potentials (higher SOD and CAT enzymes) and decreased MDA (lipid peroxidation) levels in their wound tissue homogenates. Hydroxyproline amino acid (collagen) was significantly up-regulated by CCS treatment, which is commonly related to faster wound closure area. The outcomes suggest CCS as a viable new source of pharmaceuticals for wound treatment.

Sinomenine accelerate wound healing in rats by augmentation of antioxidant, anti-inflammatory, immunuhistochemical pathways.

Sinomenine (SN) is a well-documented unique plant alkaloid extracted from many herbal medicines. The present study evaluates the wound healing potentials of SN on dorsal neck injury in rats. A uniform cut was created on Sprague Dawley rats (24) which were arbitrarily aligned into 4 groups receiving two daily topical treatments for 14 days as follows: A, rats had gum acacia; B, rats addressed with intrasite gel; C and D, rats had 30 and 60 mg/ml of SN, respectively. The acute toxicity trial revealed the absence of any toxic signs in rats after two weeks of ingestion of 30 and 300 mg/kg of SN. SN-treated rats showed smaller wound areas and higher wound closure percentages compared to vehicle rats after 5, 10, and 15 days of skin excision. Histological evaluation of recovered wound tissues showed increased collagen deposition, fibroblast content, and decreased inflammatory cells in granulated tissues in SN-addressed rats, which were statistically different from that of gum acacia-treated rats. SN treatment caused positive augmentation of Transforming Growth Factor Beta 1 (angiogenetic factor) in wound tissues, denoting a higher conversion rate of fibroblast into myofibroblast (angiogenesis) that results in faster wound healing action. Increased antioxidant enzymes (SOD and CAT), as well as decreased MDA contents in recovered wound tissues of SN-treated rats, suggest the antioxidant potentials of SN that aid in faster wound recovery. Wound tissue homogenates showed higher hydroxyproline amino acid (collagen content) values in SN-treated rats than in vehicle rats. SN treatment suppressed the production of pro-inflammatory cytokines and increased anti-inflammatory cytokines in the serum of wounded rats. The outcomes present SN as a viable pharmaceutical agent for wound healing evidenced by its positive modulation of the antioxidant, immunohistochemically proteins, hydroxyproline, and anti-inflammatory cytokines.

Boric Acid (Boron) Attenuates AOM-Induced Colorectal Cancer in Rats by Augmentation of Apoptotic and Antioxidant Mechanisms.

Boric acid (BA) is a naturally occurring weak Lewis acid containing boron, oxygen, and hydrogen elements that can be found in water, soil, and plants. Because of its numerous biological potentials including anti-proliferation actions, the present investigates the chemopreventive possessions of BA on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty laboratory rats were divided into 5 groups: negative control (A) received two subcutaneous inoculations of normal saline and nourished on 10% Tween 20; groups B-E had two injections of 15 mg/kg azoxymethane followed by ingestion of 10% Tween 20 (B, cancer control), inoculation with intraperitoneal 35 mg/kg 5-fluorouracil injection (C, reference group), or ingested with boric acid 30 mg/kg (D) and 60 mg/kg (E). The gross morphology results showed significantly increased total colonic ACF in cancer controls, while BA treatment caused a significant reduction of ACF values. Histopathological evaluation of colons from cancer controls showed bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands than that of BA-treated groups. Boric acid treatment up-surged the pro-apoptotic (Bax) expression and reduced anti-apoptotic (Bcl-2) protein expressions. Moreover, BA ingestion caused upregulation of antioxidant enzymes (GPx, SOD, CAT), and lowered MDA contents in colon tissue homogenates. Boric acid-treated rats had significantly lower pro-inflammatory cytokines (TNF-α and IL-6) and higher anti-inflammatory cytokines (IL-10) based on serum analysis. The colorectal cancer attenuation by BA is shown by the reduced ACF numbers, anticipated by its regulatory potentials on the apoptotic proteins, antioxidants, and inflammatory cytokines originating from AOM-induced oxidative damage.

Ethnobotanical, Phytochemistry, and Pharmacological Activity of Onosma (Boraginaceae): An Updated Review.

The genus Onosma belongs to the Boraginaceae family and contains over 230 species. The present review sheds light on the ethnopharmacology, phytoconstituents, bioactivity, and toxicology of the Onosma species from previous investigations. Furthermore, the paper also highlights the unresolved issues for the future investigations. The review included previous studies of the genus Onosma available from Google Scholar and Baidu Scholar, Science Direct, SciFinder, Wiley Online Library, and Web of Science. Until now, more than 200 chemical compounds have been detected from the genus Onosma, including naphthoquinone (33), flavonoids (30), hydrocarbon (23), phenolic (22), ester (17), alkaloids (20), aromatics (12), carboxylic acid (11), fatty acids (9), terpenoids (10), while the most important ones are rosmarinic, ferulic, protocatechuic, chlorogenic, caffeic, p-coumaric acids, and apigenin. The Onosma species are reported as traditional medicine for wound healing, heart disease, and kidney disorders, while the pharmacological investigations revealed that the extracts and the phytochemicals of Onosma species have different therapeutic properties including antioxidant, enzyme inhibitory, antitumor, hepatoprotective, antiviral, anti-inflammatory, and antimicrobial actions. The summarized knowledge in this review provides valuable ideas for the current and future drug discovery and a motivation for further investigation on the genus Onosma.

Green Synthesis of Silver Nanoparticles from Aqueous Extract of Tinospora crispa Stems Accelerate Wound Healing in Rats.

GRAPHICAL ABSTRACT: [Formula: see text].