Chemometrics-Assisted Identification of Anti-Inflammatory Compounds from the Green Alga Klebsormidium flaccidum var. zivo

Abstract

The green alga Klebsormidium flaccidum var. zivo is a rich source of proteins, polyphenols, and bioactive small-molecule compounds. An approach involving chromatographic fractionation, anti-inflammatory activity testing, ultrahigh performance liquid chromatography-mass spectrometry profiling, chemometric analysis, and subsequent MS-oriented isolation was employed to rapidly identify its small-molecule anti-inflammatory compounds including hydroxylated fatty acids, chlorophyll-derived pheophorbides, carotenoids, and glycoglycerolipids. Pheophorbide a, which decreased intracellular nitric oxide production by inhibiting inducible nitric oxide synthase, was the most potent compound identified with an IC50 value of 0.24 µM in lipopolysaccharides-induced macrophages. It also inhibited nuclear factor kappaB activation with an IC50 value of 32.1 µM in phorbol 12-myristate 13-acetate-induced chondrocytes. Compared to conventional bioassay-guided fractionation, this approach is more efficient for rapid identification of multiple chemical classes of bioactive compounds from a complex natural product mixture.

Brown Macroalgae Sargassum cristaefolium Extract Inhibits Melanin Production and Cellular Oxygen Stress in B16F10 Melanoma Cells

“…This porphyrin derivative was discovered earlier in the brown algae Saccharina japonica (former name Laminaria japonica ), where it inhibited NO generation in LPS-stimulated RAW 264.7 cells [ 47 ]. This anti-inflammation component was also discovered in the green algae Klebsormidium flaccidum [ 48 ].…”

Chemometric‐based drug discovery approaches from natural origins using hyphenated chromatographic techniques

“…43,44 Chemometric methods could be applied as appropriate tools for every step of natural products biochemomteric research, including experiment design, data pre-processing, metabolite identification, variable selection, and modeling, 45 that offers an efficient route to meaningful interpretation of results in biochemometric. 35 Particularly, biochemometric has been reported for the detection of active agents with different bio-and chemical-activities, for example, antioxidant, [46][47][48][49][50][51][52][53][54] cytotoxic, 27,[55][56][57] and anti-inflammatory effects, [58][59][60][61] in addition to α-amylase and α-glucosidase and tyrosinase inhibitions, 57,[62][63][64][65][66] and vasorelaxant, 67 anthelmintic, 68 antidiabetic, 69 and phytotoxic 70 properties. List of published articles on biological activities using metabolomics as well as chemometric tools is presented in Tables 1-3.…”

“…60 Another approach involving column chromatographic fractionation subsequent to HPLC-MS profiling, anti-inflammatory activity, and subsequent biochemometric analysis (e.g., OPLS-DA), oriented isolation in order to identify small-molecules with anti-inflammatory activities in green alga Klebsormidium flaccidum Kützing. 58 This method was proven to be more effective for quickly identifying chemically bioactive molecules from a complicated mixture of natural products than traditional bioassay-guided fractionation.…”

“…180 The traditional HPLC method has been replaced with UPLC fingerprints of herbal compounds. 58,67,99,181 For instance, fingerprints of Aconitum carmichaelii Debeaux (Fuzi) and its processed products including Yanfuzi, Heishunpian, and Paofupian were established by UPLC and their effects on rat's liver mitochondrial metabolism determined using microcalorimetry. Spectrum-effect relationships between UPLC fingerprints and energy metabolism of mitochondria were explored The botanical name was not reported on the original article.…”

“…Particularly, biochemometric has been reported for the detection of active agents with different bio‐ and chemical‐activities, for example, antioxidant, 46–54 cytotoxic, 27,55–57 and anti‐inflammatory effects, 58–61 in addition to α ‐amylase and α ‐glucosidase and tyrosinase inhibitions, 57,62–66 and vasorelaxant, 67 anthelmintic, 68 antidiabetic, 69 and phytotoxic 70 properties. List of published articles on biological activities using metabolomics as well as chemometric tools is presented in Tables 1–3.…”