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Ambrosia maritima L. (family Asteraceae) is an annual herb widely distributed throughout the Mediterranean region and Africa. The herb is employed in folk medicine for the treatment of many ailments. Herein, we report a comprehensive investigation of the diverse biological potential of two sesquiterpene lactones, damsin and neoambrosin, isolated from Ambrosia maritima. 1D and 2D NMR and HR-ESI-MS/MS were employed to characterize the chemical structures of both compounds. In order to identify biological targets of both compounds we investigated their potential affinity for peroxisome proliferator-activated receptors (PPARs) and transient receptor potential (TRP) channels, which are pleiotropic classes of receptors implicated in essential functions of the body. This was investigated using a luciferase assay and a calcium fluorometric assay. A carbonic anhydrase inhibition assay was also performed using stopped flow CO 2 hydrase spectrophotometric assay. Our analysis revealed that unlike damsin, neoambrosin showed a selective partial agonist effect on PPARγ receptors and TRPA1 channels. Its binding mode was investigated through in silico analysis. Both compounds showed no affinity for the tested carbonic anhydrases. Overall, our study details the chemical properties of neoambrosin and damsin and highlights neoambrosin as novel, cost-effective partial agonist of PPARɣ and TRPA1 receptors despite additional in vivo studies are needed to elucidate its biological and pharmacological properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Scientific publications documented the use of plants from Genus Malva to treat inflammatory diseases and skin disorders by our ancestors. Malva parviflora L. has reported benefits for wound healing in traditional medicine; however, there is a lack of experimental study to validate these claims., Aim: We initiated this study to explore the metabolites and verify the wound healing properties of M. parviflora using in vivo and in vitro models., Materials and Methods: Liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was used to identify the ethanolic extract different metabolites. Additionally, total phenolic content was determined using Folin-Ciocalteu reagent. To verify the extract wound healing potential, an in vivo rat wound excision model was employed. Round wounds (5 mm in diameter) were created by a sterile biopsy punch needle. The wounds were treated with plant extracts (2.5% and 5%) as well as a commercially available wound healing product (Mebo®) for 10 days. The results were assessed as follows: 1) Measuring the reduction% in wound area compared to the original wound size. 2) Evaluation of the levels of wound healing biomarkers, namely collagen type I (Col-1), alpha smooth muscle actin (α-SMA), extracellular signal-regulated kinases-1 (ERK1), and matrix metalloproteinase-9 (MMP9) levels. 3) Performing histopathological examination of the wound tissue. The antioxidant properties of the M. parviflora leaves ethanolic extract were investigated using various assays: total antioxidant capacity (TAC), iron reducing power (IRP), 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals scavenging assays. Furthermore, the anti-inflammatory activity was confirmed by calculating the inhibition percentages of protein denaturation and the activity of the proteinase enzyme., Results: Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis revealed the presence of various secondary metabolites in M. parviflora ethanolic extract, including phenolic acids (cinnamic and ferulic acids), flavonoids (quercetin and "iso"rhamnetin monoglucuronides), fatty acids (hydroxy-octadecatrienoic and oxo-octadecatrienoic acids), in addition to chlorophyll derivatives and carotenoids (pheophorbide-a and lutein, respectively). Malva extracts significantly reduced wound size compared to untreated control group. The extracts also promoted wound healing by upregulating collagen I, α-SMA, and ERK1 levels, while downregulating MMP9 expression. Notably, the effect of 2.5% and 5% extracts was similar or exceeds those of Mebo®, supported by histopathological results. Finally, M. parviflora ethanolic extract exhibited antioxidant and anti-inflammatory potentials comparable to the used standards., Conclusion: Our study provides evidence-based support for the wound healing properties of M. parviflora L. leaves ethanolic extract. This is further strengthened by the fact that many of the identified metabolites possess wound healing, antioxidant, and/or anti-inflammatory activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacologial Relevance: Although Damsissa (Ambrosia maritima) is traditionally used as anti-inflammatory and diuretic, the biological activity and mechanism of action of its major constituents are to be elucidated., Aim: to decipher the anti-arthritic potential of damsin (DMS) and neoambrosin (NMS) and to unfold their molecular signaling in complete Freund's adjuvant (CFA)-induced arthritis model., Materials and Methods: the right hind paw was inoculated with CFA (0.1 ml) at day 0 and 7 while treatments were started from the 14 th day and continued for 2 weeks. Rats were randomly assigned into 4 groups; normal group (NRML), CFA-induced arthritis group, CFA-induced arthritis treated with DMS and NMS (10 mg/kg/day) as 3 rd and 4 th group; respectively., Results: Throughout experimental period, treatments ameliorated the increase of paw volume, knee joint diameter and nociception tests as reflected in open field arena. Also, DSM and NMS suppressed phosphorylation of Akt, STAT-3, ERK1/2 which was further mirrored by inactivation of GSK3β and downregulation of MCP-1 together with CCN1 and NF-kβ in hind paw tissue. Concomitantly, inflammation markers; TNF-α, IL-6, -12 were lowered as confirmed microscopically during examination of hind paw tissue., Conclusion: DSM and NMS-induced suppression of NF-kβ subdues clinical features of RA most probably through repression of Akt/ERK1/2/STAT3 pathway. Therefore, DMS and NMS can serve as safe and effective treatment for rheumatoid arthritis, one of the most disabling chronic, inflammatory and painful autoimmune disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)