Bioengineering of Anti‐Inflammatory Natural Products

Winand, Lea; Sester, Angela; Nett, Markus

doi:10.1002/cmdc.202000771

Cited by 21 publications

(15 citation statements)

References 130 publications

(349 reference statements)

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“…This situation stimulates the search for new molecules aiming at safer drugs with low side-effects for the inflammation treatment [ 8 , 9 ]. The mechanisms involved in the inflammatory response are fundamental for anti-inflammatory drug development [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Chemical Characterization of Flowers and Leaf Extracts Obtained from Turnera subulata and Their Immunomodulatory Effect on LPS-Activated RAW 264.7 Macrophages

et al. 2022

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The anti-inflammatory properties of Turnera subulata have been evaluated as an alternative drug approach to treating several inflammatory processes. Accordingly, in this study, aqueous and hydroalcoholic extracts of T. subulata flowers and leaves were analyzed regarding their phytocomposition by ultrafast liquid chromatography coupled to mass spectrometry, and their anti-inflammatory properties were assessed by an in vitro inflammation model, using LPS-stimulated RAW-264.7 macrophages. The phytochemical profile indicated vitexin-2-O-rhamnoside as an important constituent in both extracts, while methoxyisoflavones, some bulky amino acids (e.g., tryptophan, tyrosine, phenylalanine), pheophorbides, and octadecatrienoic, stearidonic, and ferulic acids were detected in hydroalcoholic extracts. The extracts displayed the ability to modulate the in vitro inflammatory response by altering the secretion of proinflammatory (TNF-α, IL-1β, and IL-6) and anti-inflammatory (IL-10) cytokines and inhibiting the PGE-2 and NO production. Overall, for the first time, putative compounds from T. subulata flowers and leaves were characterized, which can modulate the inflammatory process. Therefore, the data highlight this plant as an option to obtain extracts for phytotherapic formulations to treat and/or prevent chronic diseases.

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Section: Introductionmentioning

confidence: 99%

Chemical Characterization of Flowers and Leaf Extracts Obtained from Turnera subulata and Their Immunomodulatory Effect on LPS-Activated RAW 264.7 Macrophages

et al. 2022

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“…In recent years, traditional medicine has become a source of new pharmaceuticals due to their strong efficacy with fewer side effects and lower toxicity, and have made surprising progress in the treatment of various diseases, such as tumors, inflammation, gout, atherosclerosis, virus infection, bacterial infection and fungal infection [16][17][18][19][20][21][22]. Tibetan medicine, as an important traditional medicine, has unique advantages in the treatment of peptic ulcers.…”

Section: Discussionmentioning

confidence: 99%

The tibetan medicine Zuozhu-Daxi can prevent Helicobacter pylori induced-gastric mucosa inflammation by inhibiting lipid metabolism

et al. 2022

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Background Tibetan medicine has been used in clinical practice for more than 3800 years. Zuozhu-Daxi (ZZDX), a classic traditional Tibetan medicine, has been proved to be effective in the treatment of digestive diseases, such as chronic gastritis, gastric ulcer, etc. Helicobacter pylori (H. pylori), one of the most common pathogenic microbes, is regarded as the most common cause of gastritis. Researching on the effects of ZZDX on H. pylori-induced gastric mucosa inflammation could provide more evidences on H. pylori treatment and promote the development of Tibetan medicine. This study aimed to explore whether ZZDX could rescue H. pylori-induced gastric mucosa inflammation and its mechanism. Methods Male C57BL/6 mice were infected with H. pylori, and orally treated with ZZDX to rescue gastric mucosa inflammation induced by H. pylori infection. Pathology of gastric mucosa inflammation was evaluated under microscopy by hematoxylin–eosin (HE) staining. The infection status of H. pylori was evaluated by immunohistochemical (IHC) staining. The reactive oxygen species (ROS) level in serum was evaluated using a detection kit. IL-1α, IL-6, and PGE2 expression levels in serum were measured using ELISA. IL-1α, IL-8, TNF-α, and NOD1 expression levels in gastric tissues were measured using real-time PCR. RNA sequencing and gene certification of interest were performed to explore the mechanisms in vivo and in vitro. Results The results showed that ZZDX could significantly inhibit H. pylori-induced gastric mucosa inflammation using HE staining. IL-1α, IL-6, and PGE2 expression levels in serum were significantly decreased after treatment with ZZDX. ZZDX treatment significantly decreased the mRNA expression of IL-8 induced by H. pylori infection in gastric tissues. Elovl4, Acot1 and Scd1 might be involved in the mechanisms of ZZDX treatment. However, the H. pylori infection status in the gastric mucosa was not reduced after ZZDX treatment. Conclusions ZZDX reversed gastric mucosal injury and alleviated gastric mucosa inflammation induced by H. pylori infection.

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“…Although it is in theory possible to abolish HMQ production in a native producer by targeted gene inactivation and to produce the desired derivatives of aurachin D by mutasynthesis, this approach will also result in a complex product spectrum due to subsequent biosynthetic transformations of the AuaA product (Pistorius et al 2011 ). To circumvent an extensive downstream processing, it seems advisable to carry out the prenylation reaction by biotransformation (Winand et al 2021 ) using a heterologous host expressing auaA . An in vitro prenylation with purified AuaA would be another alternative, but this option requires the addition of FPP as a cosubstrate.…”

Section: Introductionmentioning

confidence: 99%

Biocatalytic production of the antibiotic aurachin D in Escherichia coli

2022

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Aurachin D is a potent inhibitor of cytochrome bd oxidases, which are potential targets in the treatment of infectious diseases. In this study, our aim was to improve the biocatalytic production of aurachin D from a quinolone precursor molecule with recombinant Escherichia coli cells expressing the biosynthesis enzyme AuaA. In order to achieve a high-level production of this membrane-bound farnesyltransferase in E. coli, the expression of the auaA gene was translationally coupled to an upstream cistron in accordance with a bicistronic design (BCD) strategy. Screening of various BCD elements led to the identification of optimized auaA expression cassettes, which increased the aurachin D titer in E. coli up to 29-fold in comparison to T7-mediated expression. This titer could be further raised by codon optimization of auaA and by introducing the mevalonate pathway into the production strain. The latter measure was intended to improve the availability of farnesyl pyrophosphate, which is needed as a cosubstrate for the AuaA-catalyzed reaction. In sum, the described efforts resulted in a strain producing aurachin D with a titer that is 424 times higher than that obtained with the original, non-optimized expression host. Graphical Abstract

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Bioengineering of Anti‐Inflammatory Natural Products

Cited by 21 publications

References 130 publications

Chemical Characterization of Flowers and Leaf Extracts Obtained from Turnera subulata and Their Immunomodulatory Effect on LPS-Activated RAW 264.7 Macrophages

Chemical Characterization of Flowers and Leaf Extracts Obtained from Turnera subulata and Their Immunomodulatory Effect on LPS-Activated RAW 264.7 Macrophages

The tibetan medicine Zuozhu-Daxi can prevent Helicobacter pylori induced-gastric mucosa inflammation by inhibiting lipid metabolism

Biocatalytic production of the antibiotic aurachin D in Escherichia coli

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