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Inflammation that is not resolved in due course becomes a chronic disease. The treatment of chronic inflammatory diseases involves a long-term use of anti-inflammatory drugs such as corticosteroids and nonsteroidal anti-inflammatory drugs, often accompanied by dose-dependent side effects. Local drug delivery systems have been widely explored to reduce their off-target side effects and the medication frequency, with several products making to the market or in development over the years. However, numerous challenges remain, and drug delivery technology is underutilized in some applications. This review showcases local drug delivery systems in different inflammatory diseases, including the targets well-known to drug delivery scientists (e.g., joints, eyes, and teeth) and other applications with untapped opportunities (e.g., sinus, bladder, and colon). In each section, we start with a brief description of the disease and commonly used therapy, introduce local drug delivery systems currently on the market or in the development stage, focusing on polymeric systems, and discuss the remaining challenges and opportunities in future product development.
Minthostachys verticillata (Griseb.) Epling (Lamiaceae), known as Peperina is a medicinal native plant, with a traditional use as a digestive, antispasmodic and antidiarrheic.
Despite its folkloric use, no scientific evaluation of this plant related to the gastrointestinal inflammatory process has been carried out to date. The present study aims to assess the effects of M. verticillata on gastrointestinal system in experimental models.
M. verticillata (250 and 500mg/kg) was orally tested in a colitis model induced by acetic acid. Colon weight/length ratio, oxidative stress (oxidized and reduced glutathione), histological changes using Alcian blue and hematoxylin & eosin staining and expression of IL1β, TNFα, iNOS, COX-2 were evaluated. The effect of the extract in three additional in vivo models were studied intestinal motility and diarrhea induced by ricin oil, and visceral pain induced by intracolonic administration of capsaicin. Finally, the activity on concentration response curves of acetylcholal pathophysiology of inflammatory bowel disease.
This is the first study to validate traditional use of M. verticillata for digestive disorders and demonstrated that its aqueous extract could represent a promising strategy in targeting the multifactorial pathophysiology of inflammatory bowel disease.
EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease.
Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects.
Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model.
Scopolagnitive impairment rat without alteration in their systemic/brain exposure.
Ganoderma lucidum (G. lucidum, Lingzhi), also known as "immortality mushroom" has been broadly used to improve health and longevity for thousands of years in Asia. G. lucidum and its spores have been used to promote health, based on its broad pharmacological and therapeutic activity. This species is recorded in Chinese traditional formula as a nootropic and has been suggested to improve cognitive dysfunction in Alzheimer's disease. However, little is known about the nootropic effects and molecular mechanism of action of G. lucidum spores.
The present study investigated the protective effects of sporoderm-deficient Ganoderma lucidum spores (RGLS) against learning and memory impairments and its mechanism of action.
In the Morris water maze, the effects of RGLS on learning and memory impairments were evaluated in a rat model of sporadic Alzheimer's disease that was induced by an intracerebroventricular injection of streptozotocin (STZ). Changes in amyloid β (Aβ) expression, Tau expression and phosphorylaticts depended on a decrease in Aβ expression and Tau hyperphosphorylation and the modulation of BDNF-TrkB signaling in the hippocampus.
Poria cocos (Schw.) Wolf (Poria) is a well-known traditional medicinal fungus. It has been considered to possess spleen-invigorating (Jianpi) effects in traditional Chinese medicine, and is used clinically to treat spleen deficiency (Pixu) with symptoms of intestinal disorders such as diarrhea, indigestion, mucositis and weight loss.
To investigate the protective effects of Poria and its three component fractions (Water-soluble polysaccharides, WP; alkali-soluble polysaccharides, AP; triterpene acids, TA) on cisplatin-induced intestinal injury and explore the underlying mechanisms.
C57BL/6 mice were treated with Poria powder (PP), WP, AP and TA by oral gavage respectively for 13 days, and intraperitoneally injected with 10mg/kg of cisplatin on day 10 to conduct a cisplatin-induced intestinal injury model. Pathological changes of ileum and colon were examined using H&E staining. The composition of gut microbiota and the alteration of host metabolites were characterized by 16S rDNA amplicon sequencingut microbiota and metabolic profiles.
PP and WP possess protective effects against cisplatin-induced intestinal injury via potentially regulating the gut microbiota and metabolic profiles.
Ferula sinkiangensis K. M. Shen is a traditional Chinese medicine that has a variety of pharmacological properties relevant to neurological disorders and inflammations. https://www.selleckchem.com/products/dbet6.html Kellerin, a novel compound extracted from Ferula sinkiangensis, exerts a strong anti-neuroinflammatory effect by inhibiting microglial activation. Microglial activation plays a vital role in ischemia-induced brain injury. However, the potential therapeutic effect of kellerin on focal cerebral ischemia is still unknown.
To explore the effect of kellerin on cerebral ischemia and clarify its possible mechanisms, we applied the middle cerebral artery occlusion (MCAO) model and the LPS-activated microglia model in our study.
Neurological outcome was examined according to a 4-tiered grading system. Brain infarct size was measured using TTC staining. Brain edema was calculated using the wet weight minus dry weight method. Neuron damage and microglial activation were observed by immunofluorescence in MCAO model in rats. In in vitro studies, microglial activation was examined by flow cytometry and the viability of neuronal cells cultured in microglia-conditioned medium was measured using MTT assay.
