Potent nitric oxide inhibitory sesquiterpenoids from the rhizome of Curcuma aromatica Salisb.

One new sesquiterpenoid, curcaromatin (1), together with twenty-one known compounds 2-22, were isolated from the rhizomes of Curcuma aromatica Salisb. (Zingiberaceae). Their structures were established by extensive spectroscopic (1D and 2D NMR and HR-MS) analysis. Most of the isolated compounds were investigated for nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells. (-)-Xanthorrhizol (3) displayed the strongest NO inhibitory activity with an IC50 value of 4.3 µM, which was 3.7-fold more active than the reference compound, aminoguanidine (IC50 15.9 µM). The selectivity index (SI > 28.1) of compound 3 was almost 3-fold higher than that of aminoguanidine.

Protective effects of Stephania pierrei tuber-derived oxocrebanine against LPS-induced acute lung injury in mice.

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) have high mortality rates. Though corticosteroids are commonly used for the treatment of these conditions, their efficacy has not been conclusively demonstrated and their use can induce various adverse reactions. Hence, the application of corticosteroids as therapeutic modalities for ALI/ARDS is limited. Meanwhile, the aporphine alkaloid oxocrebanine isolated from Stephania pierrei tubers has demonstrated anti-inflammatory efficacy in murine/human macrophage cell lines stimulated by lipopolysaccharide (LPS). Accordingly, the primary objectives of the present study are to investigate the anti-inflammatory effects of oxocrebanine on LPS-induced murine alveolar epithelial (MLE-12) cells and its efficacy against LPS-induced murine ALI. Results show that oxocrebanine downregulates the abundance of interleukin (IL)-1beta, IL-6, and inducible nitric oxide synthase, as well as the phosphorylation of nuclear factor-kappaB (NF-κB), stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), p38, protein kinase B (Akt), and glycogen synthase kinase-3beta signalling proteins in LPS-induced MLE-12 cells. Moreover, in a murine ALI model, oxocrebanine lowers lung injury scores and lung wet/dry weight ratios while reducing inflammatory cell infiltration. It also suppresses LPS-induced tumour necrosis factor-alpha and IL-6 in the bronchoalveolar lavage fluid and plasma. Moreover, oxocrebanine downregulates NF-κB, SAPK/JNK, p38, and Akt phosphorylation in the lung tissues of LPS-treated mice. Taken together, the foregoing results show that oxocrebanine provides significant protection against LPS-induced ALI in mice primarily by suppressing various inflammatory signalling pathways in alveolar epithelial cells and lung tissues. Hence, oxocrebanine might prove effective as an anti-inflammatory agent for the treatment of lung inflammation.

Trihydroxyxanthones from the heartwood of Maclura cochinchinensis modulate M1/M2 macrophage polarisation and enhance surface TLR4.

The anti-inflammatory actions of phytochemicals have attracted much attention due to the current state of numerous inflammatory disorders. Thai traditional medicine uses Maclura cochinchinensis (Lour.) Corner to treat chronic fever and various inflammatory diseases, as well as to maintain normal lymphatic function. Five flavonoids and five xanthones were isolated from the heartwood of M. cochinchinensis and we investigated the anti-inflammatory properties of the isolated compounds. All isolated compounds possessed an anti-inflammatory effect by decreasing prostaglandin E2 (PGE2) synthesis in lipopolysaccharide (LPS)-activated murine macrophages with varying degrees of potency. The greatest decrease in M1 inflammatory mediators, nitric oxide, PGE2, and proinflammatory cytokines was observed with 1,3,7-trihydroxyxanthone and 1,3,5-trihydroxyxanthone treatment of LPS-activated macrophages. The anti-inflammatory mechanism of the two xanthones is mediated by the suppression of inducible nitric oxide synthase, cyclooxygenase-2, and phosphatidylinositol 3-kinase/protein kinase B expression and the upregulation of M2 anti-inflammatory signalling proteins phosphorylated signal transducer and activator of transcription 6 and peroxisome proliferator-activated receptors-γ. 1,3,7-Trihydroxyxanthone exhibits superior induction of anti-inflammatory M2 mediator of LPS-activated macrophages by upregulating arginase1 expression. Following the resolution of inflammation, the two xanthones enhanced surface TLR4 expression compared to LPS-stimulated cells, possibly preserving macrophage function. Our research highlights the role of the two xanthones in modulating the M1/M2 macrophage polarisation to reduce inflammation and retain surface TLR4 once inflammation has been resolved. These findings support the use of xanthones for their anti-inflammatory effects in treating inflammatory dysregulation.

Therapeutic deep eutectic solvent-based microemulsion enhances anti-inflammatory efficacy of curcuminoids and aromatic-turmerone extracted from Curcuma longa L.

To diminish chemical waste and improve the delivery of Curcuma longa L. (CL) constituents, microemulsions based on hydrophobic deep eutectic solvents (HDESs) were designed as ready-to-use solvents for CL extraction. The microemulsion (ME) of the ME-23 formulation (HDES/Tween 80 : propylene glycol (1 : 1)/water, 25/70/5) displayed CL extraction yields of 1.69, 3.04, 7.36, and 1.39 wt% of bisdemethoxycurcumin, demethoxycurcumin, curcumin, and aromatic-turmerone, respectively. The ME-23 without CL chemical constituents and ME-23-based CL extract inhibited NO production with an IC50 value of 0.0136 ± 0.0023%v/v and a curcumin IC50 value of 75.2 ± 6.7 nM, respectively, and simultaneously lowered inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß production in lipopolysaccharide-activated murine macrophages. Authentic curcumin in ME-23 possessed superior NO inhibitory activity, which was 103-fold more effective than curcumin prepared in the conventional solvent dimethyl sulfoxide. ME-23 was also capable of delivering curcumin into murine macrophages. After 30 days of storage in HDES and HDES-based ME, curcumin remained more than 90%. ME-23 provides advantages for CL extraction, constituent delivery, and anti-inflammatory functions that can be applied to pharmaceutical and cosmetic products.

Oxocrebanine from Stephania pierrei exerts macrophage anti-inflammatory effects by downregulating the NF-κB, MAPK, and PI3K/Akt signalling pathways.

Plant-derived medicinal compounds are increasingly being used to treat acute and chronic inflammatory diseases, which are generally caused by aberrant inflammatory responses. Stephania pierrei Diels, also known as Sabu-lueat in Thai, is a traditional medicinal plant that is used as a remedy for several inflammatory disorders. Since aporphine alkaloids isolated from S. pierrei tubers exhibit diverse pharmacological characteristics, we aimed to determine the anti-inflammatory effects of crude extracts and alkaloids isolated from S. pierrei tubers against lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Notably, the n-hexane extract strongly suppressed nitric oxide (NO) while exhibiting reduced cytotoxicity. Among the five alkaloids isolated from the n-hexane extract, the aporphine alkaloid oxocrebanine exerted considerable anti-inflammatory effects by inhibiting NO secretion. Oxocrebanine also significantly suppressed prostaglandin E2, tumour necrosis factor-α, interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase, and cyclooxygenase (COX)-2 protein expression by inactivating the nuclear factor κB, c-Jun NH2-terminal kinase, extracellular signal-regulated kinase 1/2, and phosphatidylinositol 3-kinase/Akt inflammatory signalling pathways. Molecular docking analysis further revealed that oxocrebanine has a higher affinity for toll-like receptor 4/myeloid differentiation primary response 88 signalling targets and the COX-2 protein than native ligands. Thus, our findings highlight the potential anti-inflammatory effects of oxocrebanine and suggest that certain alkaloids of S. pierrei could be used to treat inflammatory diseases.

Marginaols G-M, anti-inflammatory isopimarane diterpenoids, from the rhizomes of Kaempferia marginata.

Marginaols G-M, a series of undescribed isopimarane diterpenoids, together with four known analogs were isolated from the rhizomes of Kaempferia marginata. The structures of these isolated compounds were characterized using high-resolution mass spectrometry and extensive 1D- and 2D-nuclear magnetic resonance (NMR) analyses. In addition, the absolute configurations of marginaol G and H were determined by X-ray crystallographic analysis and comparison with the literature values. When compared to the standard drug dexamethasone (IC50 4.7 µM), marginaol G, H, and 6ß-acetoxysandaracopimaradien-1α,9α-diol had an intriguing anti-inflammatory effect on NO inhibition in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with IC50 values ranging from 4.5 to 7.3 µM and being less cytotoxic to the cells. The anti-inflammatory action of these isopimarane diterpenoids from K. marginata supports the use of Thai traditional medicine for inflammation treatment.

1,7­Bis(4­hydroxy­3­methoxyphenyl)­1,4,6­heptatrien­3­one alleviates lipopolysaccharide­induced inflammation by targeting NF­κB translocation in murine macrophages and it interacts with MD2 in silico.

Trienones are curcuminoid analogues and are minor constituents in the rhizomes of numerous Curcuma plant species. Studies investigating the biological activities of trienones, particularly their anti­inflammatory activities, are limited. In the present study, the trienone 1,7­bis(4­hydroxy­3­methoxyphenyl)­1,4,6­heptatrien­3­one (HMPH) was structurally modified from curcumin using a novel and concise method. HMPH was shown to exhibit potential anti­inflammatory effects on lipopolysaccharide (LPS)­activated RAW264.7 macrophages. Furthermore, LPS­induced nitric oxide secretion in RAW264.7 cells was markedly and dose­dependently inhibited by HMPH; in addition, HMPH had a greater efficacy compared with curcumin. This inhibition was accompanied by the suppression of inducible nitric oxide synthase and cyclooxygenase­2 expression, as well as pro­inflammatory cytokine secretion. To elucidate the molecular mechanism underlying the anti­inflammatory effects of HMPH, the effects of this compound on nuclear factor­κB (NF­κB) translocation were assessed. HMPH significantly inhibited the translocation of p65 NF­κB into the nucleus to a greater extent than curcumin, thus indicating that HMPH has more potent anti­inflammatory activity than curcumin. In addition, an in silico modelling study revealed that HMPH possessed stronger binding energy to myeloid differentiation factor 2 (MD2) compared with that of curcumin, and indicated that the anti­inflammatory effects of HMPH may be through upstream inhibition of the inflammatory pathway. In conclusion, HMPH may be considered a promising compound for reducing inflammation via targeting p65 NF­κB translocation and interfering with MD2 binding.

Malondialdehyde as a Useful Biomarker of Low Hand Grip Strength in Community-Dwelling Stroke Patients.

The assessment of muscle strength by hand grip strength (HGS) is used to evaluate muscle weakness and wasting among stroke patients. This study aimed to investigate the association of oxidative stress/oxidative damage and inflammatory biomarkers with muscle strength and wasting, as evaluated by HGS, among community-dwelling post-stroke patients. The HGS of both paretic and non-paretic limbs was negatively associated with modified Rankin scale (mRS) values. The serum levels of catalase activity and malondialdehyde (MDA), and plasma tumor necrosis factor (TNF)-α levels were significantly increased in post-stroke patients compared with non-stroke controls. Further analysis highlighted that hydrogen peroxide was positively correlated with HGS in the paretic limbs. Interestingly, an elevated MDA level, excluding advanced age and high mRS, increased the risk of low HGS in the non-paretic limbs of stroke patients. This study suggests that there is a detrimental association between MDA and muscle strength and early muscle wasting among post-stroke patients. Hence, MDA is a potentially useful biomarker of muscle weakness and wasting in post-stroke patients living in the community.

New triterpenoid saponin glycosides from the fruit fibers of Trichosanthes cucumerina L.

Five new triterpenoid saponin glycosides, trichocucumerisides A-E (1-5), together with eleven known compounds (6-16) were isolated from Trichosanthes cucumerina fruit fibers. The structures of the new compounds were elucidated by detailed analysis of NMR and mass spectroscopic data as well as chemical reactions. The anti-inflammatory study against nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells shows that compounds 7 and 9 exhibited stronger NO inhibitory activity, with IC50 values of 3.0 and 2.7 µM, respectively, with comparison to positive references Celecoxib and aminoguanidine (IC50 values 75.7 and 75.0 µM, respectively). Compounds 7 and 9 also possessed a greater selectivity index (SI) of approximately 3-4-fold activity than that of the positive references.