Skin anti-aging potential of Launaea procumbens extract: Antioxidant and enzyme inhibition activities supported by ADMET and molecular docking studies.

Aging is a natural process that occurs in all living organisms. Particularly, the skin embodies aging since it serves as a barrier between the body and its surroundings. Previously, we reported the wound healing effect of Launaea procumbens and identified compounds therein. The study aims to explore the skin anti-aging properties of the plant extract. To that effect, the antioxidant potential of L. procumbens methanolic extract (LPM) was assessed using two complementary DPPH and FRAP assays. The enzyme inhibitory effect of the extract on collagenase, elastase, hyaluronidase, and tyrosinase was evaluated to assess the direct skin anti-aging effects. Similarly, the anti-inflammatory activity was evaluated to explore the indirect anti-aging effects via the assessment of extract inhibitory effects on cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). In addition, ADMET and molecular docking studies were performed to explore the interaction mechanisms of identified compounds in LPM with target enzymes. LPM demonstrated significant antioxidant activity in DPPH (IC50 = 29.08 µg/mL) and FRAP (1214.67 µM FeSO4/g extract) assays. Plant extract showed significant inhibition of collagenase, elastase, hyaluronidase, and tyrosinase (IC50 = 52.68, 43.76, 31.031, and 37.13 µg/mL, respectively). The extract demonstrated significant COX-2 and 5-LOX inhibition capacity with IC50 values of 8.635 and 10.851 µg/mL, respectively. The molecular docking study revealed the high potential of the identified compounds to bind to the active sites of enzymes crucially involved in the skin aging process. ADMET analysis of the compounds revealed their good absorption, distribution, and metabolism profiles, and they were found to be safe as well. Study findings suggest L. procumbens as a promising source for the development of natural skin anti-aging and antioxidant compounds. This, in turn, may facilitate its incorporation into cosmetic formulations after further investigation.

Effect of Launaea procumbens on thyroid glands lipid peroxidation and hormonal dysfunction: a randomized control trial.

BACKGROUND: Launaea procumbens (Roxb.) Amin is traditionally used in Pakistan for the treatment of hormonal disorders and oxidative stress. The present study was aimed to evaluate the efficacy of Launaea procumbens methanol extract (LPME) against KBrO3-induced oxidative stress and hormonal dysfunction in thyroid. METHODS: To examine the effects of LPME against the oxidative stress of KBrO3 in thyroid tissue, 36 male albino rats were used. Protective effects of LPME were observed on thyroid hormonal levels, activities of antioxidant enzymes, lipid peroxidation (TBARS) and DNA damage. RESULTS: Treatment with KBrO3 significantly (P < 0.01) reduced the levels of T3 (55.13 ± 1.93) and T4 (14.7 ± 1.78) and increased TSH (55.13 ± 1.93) levels. KBrO3 exposure in rats reduced the activities of antioxidant enzymes viz.; CAT (1.16 ± 0.08); SOD (12.0 ± 0.08), GST (17.7 ± 1.1) and GSR (54.3 ± 2.1) but increased lipid peroxidation (20.3 ± 0.71) and DNA (30.4 ± 2.0) damage. Co-administration of LPME significantly (P < 0.01) improved these alterations with respect to hormonal levels, activities of antioxidant enzymes and lipid peroxidation close to those seen in control rats. CONCLUSION: These results suggest that LPME can protect thyroid tissue against oxidative damage, possibly through the antioxidant effects of its bioactive compounds.

Antitumor characterization of various fractions of Launaea procumbens.

The antitumor activity of various six fractions of Launaea procumbens were studied using the potato disk bioassay technique. Three concentrations (10, 100, and 1000 ppm) of all these six fractions were used for characterization of antitumor activity. Among these fractions, methanolic fraction exhibited significant inhibition of crown gall tumors caused by Agrobacterium tumefaciens followed by butanolic fraction. These results revealed that methanolic and butanolic fractions contain bioactive constituents responsible for inhibition of tumor. Further purification and characterization are in progress in our laboratory.

Carbon tetrachloride-induced lipid peroxidation and hyperglycemia in rat: a novel study.

Launaea procumbens methanol extract (LPME) was evaluated against carbon tetrachloride (CCl4)-induced pancreatic oxidative damage and hyperglycemia in rats. Various doses of the extract were administered to rats after 48 h of CCl4 treatment (3 ml/kg bodyweight (bw); intraperitoneally, 20% CCl4/olive oil) twice a week for 4 weeks. Coadministration of various concentrations of LPME (100, 150 and 200 mg/kg) ameliorated the toxicity of CCl4 and reversed the serum level of enzymes (amylase and lipase), glucose and hormone (insulin). The extract was able to reduce thiobarbituric acid reactive substance but increased the glutathione contents in pancreatic tissue. Depletion of antioxidant enzyme activities (catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase and glutathione-S-reductase) and DNA damages induced with CCl4 were restored by LPME supplement. It is suggested that LPME effectively protects the liver against the CCl4-induced oxidative damage in rats, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract.

Wound Healing and Antioxidant Properties of Launaea procumbens Supported by Metabolomic Profiling and Molecular Docking.

Wounds adversely affect people's quality of life and have psychological, social, and economic impacts. Herbal remedies of Launaea procumbens (LP) are used to treat wounds. In an excision wound model, topical application of LP significantly promoted wound closure (on day 14, LP-treated animals had the highest percentages of wound closure in comparison with the other groups, as the wound was entirely closed with a closure percentage of 100%, p < 0.05). Histological analysis revealed a considerable rise in the number of fibroblasts, the amount of collagen, and its cross-linking in LP-treated wounds. Gene expression patterns showed significant elevation of TGF-ß levels (2.1-fold change after 7 days treatment and 2.7-fold change in 14 days treatment) and downregulation of the inflammatory TNF-α and IL-1ß levels in LP-treated wounds. Regarding in vitro antioxidant activity, LP extract significantly diminished the formation of H2O2 radical (IC50 = 171.6 µg/mL) and scavenged the superoxide radical (IC50 of 286.7 µg/mL), indicating antioxidant potential in a dose-dependent manner. Dereplication of the secondary metabolites using LC-HRMS resulted in the annotation of 16 metabolites. The identified compounds were docked against important wound-healing targets, including vascular endothelial growth factor (VEGF), collagen α-1, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and transforming growth factor-ß (TGF-ß). Among dereplicated compounds, luteolin 8-C-glucoside (orientin) demonstrated binding potential to four investigated targets (VEGF, interleukin 1ß, TNF-α, and collagen α-1). To conclude, Launaea procumbens extract could be regarded as a promising topical therapy to promote wound healing in excisional wounds, and luteolin 8-C-glucoside (orientin), one of its constituents, is a potential wound-healing drug lead.

Phytochemicals and Cytotoxicity of Launaea procumbens on Human Cancer Cell Lines.

BACKGROUND: The plant Launaea procumbens belongs to the family Asteraceae and traditionally used in the treatment rheumatism, kidney, liver dysfunctions and eye diseases. In the present study Phytochemical analysis and fractions of methanolic extract of L. procumbens leaves were tested in vitro for their cytotoxicity. OBJECTIVES: Phytochemical analysis and cytotoxic activity of methanolic extract and fractions of Launaea procumbens against four cancer cell lines K562, HeLa, MIA-Pa-Ca-2 and MCF-2 by SRB assay. MATERIALS AND METHODS: Powdered leaves of Launaea procumbens were extracted sequentially with hexane, ethyl acetate, butanol and water by cold extraction. Phytochemical analysis and cytotoxicity assay were carried out for these fractions using SRB assay against four human cancer cell lines, namely leukemia (K562), cervix (HeLa), pancreatic (MIA-Pa-Ca-2) and breast (MCF-7). RESULTS: Ethyl acetate extract exerts potent cytotoxicity against human leukemia (K562), cervix (HeLa) and breast (MCF-7) cell lines IC50 value of 25.30±0.50, 19.80±0.10 and 36.90±4.90 µg/ml respectively. Moderately cytotoxic effect found in hexane extract IC50 value of 41±8 and 48.20±0.50 µg/ml against leukemia (K562), and breast (MCF-7) cancer cell line respectively. The Chemical composition analyzed by GC-MS showed considerable differences in solvent fractions of Launaea procumbens. CONCLUSION: This study revealed the cytotoxic potential of ethyl acetate and hexane fractions of L. procumbens leaves on different cancer cell lines. SUMMARY: Ethyl acetate and Hexane fractions of Launaea procumbens plant exhibit cytotoxicity. Among the different fractions Ethyl acetate showed relatively higher cytotoxicity.Ethyl acetate found more cytotoxic against leukemia (K 562), cervix (HeLa) and breast (MCF-7) cancer cell lines. Moderete cytotoxicity found in hexane fraction against leukemia (K 562) and breast (MCF-7) cancer cell line.GC-MS results showed L. procumbens is a rich source of 1-H- pyrazole, 1-H-imidazole, ß -amyrin, α -amyrin and lupeol. These compounds may be attributed for the cytotoxic activity. Abbreviations used: SRB: Sulforhodamine B assay, MW: Molecular weight.

Effect of Launaea procumbens extract on oxidative marker, p53, and CYP 2E1: a randomized control study.

BACKGROUND: Ethyl acetate extracts of Launaea procumbens is used for the treatment of liver dysfunction as an herbal medicine in Pakistan. In this study, the protective effects of ethyl acetate extracts were evaluated against CCl4-induced liver injuries in rat. METHODS: To examine the protective effects against oxidative stress of carbon tetrachloride in rats, 30 male rats were equally divided into 5 groups (6 rats). Among five groups, one was treated with CCl4 (3 ml/kg i.p. in olive oil b.w.) twice a week for 4 weeks. Others were orally fed with extracts (100, 200 mg/kg b.w.), with CCl4 twice a week for 4 weeks. RESULTS: Administration of CCl4 altered the serum marker enzymes, lipid profile, CYP 2E1, p53 expression, antioxidant enzymes, nuclear organizer regions (AgNORs), and DNA. Supplement of L. procumbens ameliorated the effects of CCl4, improved CYP 2E1, p53, and increased the activities of antioxidant enzymes while activity of liver marker enzymes (ALP, ALT, AST, g-GT) and contents of lipid per oxidation contents (TBARS), AgNORs, and DNA fragmentation were decreased. Similarly body weight was increased while liver and relative liver weight was decreased with co-administration of various extracts, suggesting that L. procumbens effectively protect liver against the CCl4-induced oxidative damage in rats. CONCLUSION: The hepatoprotective and free radical scavenging effects might be due to the presence of bioactive constituents in the extract.

Evaluation for the anti-urolithiatic activity of Launaea procumbens against ethylene glycol-induced renal calculi in rats.

Launaea procumbens Linn. is a plant commonly found in the west India and has been reported to decrease the renal calculi. This study investigated the anti-urolithiatic activity of L. procumbens against ethylene glycol-induced urolithiasis and its possible underlying mechanisms. The crude methanolic extract of L. procumbens leaves was studied using ethylene glycol-induced renal calculi in rat model. Results indicate that ethylene glycol feeding to rats resulted in to hyper oxaluria, hypercalciuria, as well as increased renal excretion of phosphate. Supplementation with methanolic extract of L. procumbens leaves (MELP) significantly prevented changes in urinary calcium, oxalate and phosphate excretion dose-dependently. The increased calcium and oxalate level and number of calcium oxalate crystal in the kidney tissue of calculogenic rats were significantly reverted by supplementation with MELP. The MELP supplementation also prevents the impairment of renal functions. The mechanism underlying this effect is mediated possibly through antioxidant nephroprotection and its effect on urinary concentration of stone forming constituents and risk factor. CONCLUSION: These results indicate that methanolic extracts of L. procumbens leaves are effective against the urolithiasis.