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[Image: see text] The process of wound healing is a dynamic event that starts with inflammation, proliferation, and cell migration of various types of fibroblast cells. Therefore, identification of potential molecules which may increase the wound healing capacity of fibroblast cells is crucial. A novel hydroalcoholic formulation of belladonna (SKRIN), was developed and characterized by GC-MS/MS, DLS, TEM, and AFM and was found to contain atropine and scopolamine exhibit in aggregated nanosized particles. SKRIN-mediated fibroblast cell survival was elucidated in the presence of H(2)O(2) by MTT and flow cytometry based assays. With an EC(50) of 4.41 μg/mL, SKRIN treatment showed significant increase in cell survival that was evident from a 1.11-fold increase (p < 0.0122) in the live cell population and 4.21-fold (p < 0.0001) and 2.59-fold (p < 0.0001) reductions in the early and late apoptotic cell populations, respectively. SKRIN-mediated wound healing was measured by cell scratch assay and cell cycle analysis. During the wound closure phenomenon, SKRIN increases repairing fibroblast cell proliferation by 1.24-fold (p = 0.0481) and increases the count of G2/M phase cells by 1.76-fold (p = 0.0002) which was confirmed by increased PCNA and reduced p21 protein expressions probably mediated by molecular interactions of PCNA–p21 complex with alkaloids present in SKRIN. Relative gene expression analysis further showed that SKRIN increases the PI3K, Akt, and NF-κB expression. Our data suggests that SKRIN exhibits wound healing property by increasing cell survival and repairing fibroblast proliferation via activation of the PI3K–Akt–NF-κB pathway probably mediated by inhibition of PCNA–p21 complex interaction.

Belladonna has diverse pharmacotherapeutic properties with a shadowy history of beauty, life, and death. Alkaloids present in belladonna have anti-inflammatory, anticholinergic, antispasmodic, mydriatic, analgesic, anticonvulsant, and antimicrobial activities, which makes it widely applicable for the treatment of various diseases. However, because of its associated toxicity, the medicinal use of belladonna is debatable. Therefore, an evidence-based systematic review was planned to elucidate the pharmacotherapeutic potential of belladonna. A comprehensive literature search was performed in PubMed, MEDLINE, the Cochrane database, Embase, and ClinicalTrials.gov using the keywords "belladonna", "belladonna and clinical trials", and "safety and efficacy of belladonna". Articles published from 1965 to 2020 showing the efficacy of belladonna in diverse clinical conditions are included. The quality of evidence was generated using the GRADE approach, and 20 studies involving 2302 patients were included for the systematic review. Our analyses suggest that belladonna treatment appears to be safe and effective in various disease conditions, including acute encephalitis syndrome, urethral stent pain, myocardial ischemia injury, airway obstructions during sleep in infants, climacteric complaints, irritable bowel syndrome, and throbbing headache. However, better understanding of the dosage and the toxicity of tropane alkaloids of belladonna could make it an efficient remedy for treating diverse medical conditions.