Hyperoside as a UV Photoprotective or Photostimulating Compound-Evaluation of the Effect of UV Radiation with Selected UV-Absorbing Organic Compounds on Skin Cells.

Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective.

A Comprehensive Review on Pharmacological Activities of Pachypodol: A Bioactive Compound of an Aromatic Medicinal Plant Pogostemon Cablin Benth.

As is well known, plant products have been increasingly utilized in the pharmaceutical industry in recent years. By combining conventional techniques and modern methodology, the future of phytomedicines appears promising. Pogostemon Cablin (patchouli) is an important herb used frequently in the fragrance industries and has various therapeutic benefits. Traditional medicine has long used the essential oil of patchouli (P. cablin) as a flavoring agent recognized by the FDA. This is a gold mine for battling pathogens in China and India. In recent years, this plant has seen a significant surge in use, and approximately 90% of the world's patchouli oil is produced by Indonesia. In traditional therapies, it is used for the treatment of colds, fever, vomiting, headaches, and stomachaches. Patchouli oil is used in curing many diseases and in aromatherapy to treat depression and stress, soothe nerves, regulate appetite, and enhance sexual attraction. More than 140 substances, including alcohols, terpenoids, flavonoids, organic acids, phytosterols, lignins, aldehydes, alkaloids, and glycosides, have been identified in P. cablin. Pachypodol (C18H16O7) is an important bioactive compound found in P. cablin. Pachypodol (C18H16O7) and many other biologically essential chemicals have been separated from the leaves of P. cablin and many other medicinally significant plants using repeated column chromatography on silica gel. Pachypodol's bioactive potential has been shown by a variety of assays and methodologies. It has been found to have a number of biological activities, including anti-inflammatory, antioxidant, anti-mutagenic, antimicrobial, antidepressant, anticancer, antiemetic, antiviral, and cytotoxic ones. The current study, which is based on the currently available scientific literature, intends to close the knowledge gap regarding the pharmacological effects of patchouli essential oil and pachypodol, a key bioactive molecule found in this plant.

Pachypodol, a Methoxyflavonoid Isolated from Pogostemon cablin Bentham Exerts Antioxidant and Cytoprotective Effects in HepG2 Cells: Possible Role of ERK-Dependent Nrf2 Activation.

Oxidative stress has been implicated in the pathogenesis of many diseases including chronic liver diseases. Nrf2 is a master transcriptional factor regulating the induction of cellular antioxidant defense systems. Here, the Nrf2-activating effect of the crude methanol extract of dried leaves of Pogostemon cablin Bentham was demonstrated by measuring the antioxidant response element (ARE)-driven luciferase activity and pachypodol, 4',5-dihydroxy-3,3',7-trimethoxyflavone, was isolated by bioactivity-guided fractionation and further separation using chromatographic techniques. To our knowledge, this is the first study to evaluate the antioxidant and cytoprotective effects of pachypodol in HepG2 cells as well as the underlying molecular mechanisms. Indeed, pachypodol protected HepG2 cells from cell death caused by tert-butylhydroperoxide-induced oxidative stress and also attenuated ROS production. The ability of pachypodol to activate Nrf2/ARE pathway was further confirmed by observing Nrf2 expression in nuclear fraction, mRNA levels of Nrf2 target antioxidants, and cellular glutathione content in HepG2 cells. Extracellular signal-regulated kinase (ERK) is one of the important kinases involved in Nrf2 activation. Pachypodol increased ERK phosphorylation and ERK inhibition by PD98059 totally abrogated the increase in ARE luciferase activity, nuclear Nrf2 accumulation and mRNA levels of antioxidant enzymes by pachypodol. In conclusion, pachypodol isolated from P. cablin can protect hepatocytes from oxidative injury, possibly mediated by enhancing endogenous antioxidant defense system through ERK-dependent Nrf2 activation.

Phosphatidylinositol 4-kinase III beta is the target of oxoglaucine and pachypodol (Ro 09-0179) for their anti-poliovirus activities, and is located at upstream of the target step of brefeldin A.

In recent years, phosphatidylinositol 4-kinase III beta (PI4KB) has emerged as a conserved target of anti-picornavirus compounds. In the present study, PI4KB was identified as the direct target of the plant-derived anti-picornavirus compounds, oxoglaucine and pachypodol (also known as Ro 09-0179). PI4KB was also identified as the target via which pachypodol interferes with brefeldin A (BFA)-induced Golgi disassembly in non-infected cells. Oxysterol-binding protein (OSBP) inhibitor also has interfering activity against BFA. It seems that this interference is not essential for the anti-poliovirus (PV) activities of BFA and PI4KB/OSBP inhibitors. BFA inhibited early to late phase PV replication (0 to 6 hr postinfection) as well as PI4KB inhibitor, but with some delay compared to guanidine hydrochloride treatment. In contrast with PI4KB/OSBP inhibitors, BFA inhibited viral nascent RNA synthesis, suggesting that BFA targets some step of viral RNA synthesis located downstream of the PI4KB/OSBP pathway in PV replication. Our results suggest that PI4KB is a major target of anti-picornavirus compounds identified in vitro for their anti-picornavirus activities and for some uncharacterized biological phenomena caused by these compounds, and that BFA and PI4KB/OSBP inhibitors synergistically repress PV replication by targeting distinct steps in viral RNA replication.

Pachypodol attenuates Perfluorooctane sulphonate-induced testicular damage by reducing oxidative stress.

Perfluorooctane sulfonate (PFOS) is an endocrine disruptor chemical (EDC) with potentially adverse effects on the male reproductive system. Pachypodol (5,4'-dihydroxy-3,7,3'-trimethoxyflavone) is a promising flavonoid isolated from Pogostemon cablin (Blanco) Benth that shows a broad range of pharmacological properties. However, the potential curative effects of pachypodol on testicular toxicity are not available until now. Therefore, this research was proposed to examine the efficiency of pachypodol against PFOS-induced testicular toxicity in adult male rats. The experiments were conducted on Sprague-Dawley rats (n = 48), which were equally distributed into four groups: control, PFOS (20 mg/kg), PFOS + Pachypodol (20 mg/kg + 10 mg/kg respectively), and Pachypodol (10 mg/kg). After 56 days of treatment, testes were excised by slaughtering rats, weighed, and stored till further analysis. The estimated parameters include biochemical markers, spermatogenic indices, hormonal and histopathological profiles. PFOS exposure disturbed the biochemical profile by altering the antioxidant/oxidant balance. For instance, it decreased the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR) while increasing the concentration of reactive oxygen species (ROS) and level of thiobarbituric acid reactive substances (TBARS). PFOS intoxication also led to a notable decline in viability, motility, epididymal sperm count, and the number of HOS coiled-tail sperms, whereas the higher level of abnormality in the head, mid-piece, and tail of sperms were observed. Besides, it lowered luteinizing hormone (LH), follicle-stimulating hormone (FSH), and plasma testosterone. In addition, PFOS exposure led to histopathological damages in testicles. However, pachypodol treatment potently alleviated all the illustrated impairments in testes. Conclusively, our results demonstrate the promising free-radical scavenging activity of pachypodol, a novel phytochemical, against the PFOS-instigated testicular dysfunctions.

Cytotoxic flavonoids from the leaves of Callicarpa nudiflora hook.

A new flavonoid glycoside, luteolin-3'-O-ß-D-6″-acetyl glucopyranoside (1), along with six known flavonoids, were isolated from the leaves of Callicarpa nudiflora Hook. The structures of the isolated compounds were established on the basis of extensive spectroscopic analyses. Compound 6 exhibited potent cytotoxicity and compounds 1 and 7 exhibited moderate cytotoxicity against human hepatocellular carcinoma SMMC-7721 cells.

Pachypodol protects newborn rats from anaesthesia-induced apoptosis in the developing brain by regulating the JNK/ERK pathway.

Anaesthesia exposure causes changes in the developing brain and affects behaviour and memory. This study examined the beneficial effect of pachypodol against isoflurane (ISF)-induced neuronal injury. Seven-day-old rats were treated with 10 mg/kg and 30 mg/kg intravenous pachypodol 30 min before exposure to ISF (0.75%) for 6 h. Oxidative stress and other biochemical parameters were assessed in the brain tissue and serum using enzyme-linked immunosorbent assay. Additionally, a terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay was performed to assess neuronal cell apoptosis in several regions of the hippocampus. Cognitive function and neurological scores were determined in the pachypodol-treated neuron-injured rats. Cytokine levels and oxidative stress were reduced in the pachypodol-treated group compared with the ISF group. In addition, cognitive deterioration was reversed in pachypodol-treated compared with ISF-treated rats. Thus, treatment with pachypodol reduced neuronal apoptosis in neuron-injured rats. Moreover, pachypodol ameliorated changes to the JNK/ERK/Akt pathway in brain-injured rats. In conclusion, pachypodol treatment prevents neuronal apoptosis in ISF-treated rats by regulating the JNK/ERK pathway.

Structural Pharmacokinetics of Polymethoxylated Flavones in Rat Plasma Using HPLC-MS/MS.

The purpose of this study was to investigate the pharmacokinetics of the polymethoxylated flavonoids kumatakenin, pachypodol, and retusin, which contain two, three, or four methoxy substitutions, using a validated ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method in rats. The pharmacokinetic results demonstrated that the elimination half-lives for kumatakenin, pachypodol, and retusin were 30 ± 11.6, 39.4 ± 19.5, and 106.9 ± 26 min, respectively, for the low dose group and 54.5 ± 16.5, 33.8 ± 10, and 134.6 ± 34.7 min for the high dose group. The results suggested that the area under the curve values (AUC) for the analytes did not correlate with the number of methoxy groups. Pachypodol had the lowest AUC, which may have been correlated with lipophilicity, for both the low and high dose groups. In conclusion, the polymethoxylated flavonoid pachypodol is more hydrophilic than kumatakenin or retusin, which were correlated with the pharmacokinetic results.

Flavonoids Affect the Light Reaction of Photosynthesis in Vitro and in Vivo as Well as the Growth of Plants.

Flavonoids retusin (5-hydroxy-3,7,3',4'-tetramethoxyflavone) (1) and pachypodol (5,4'-dihydroxy-3,7,3'-trimethoxyflavone) (2) were isolated from Croton ciliatoglanduliferus Ort. Pachypodol acts as a Hill reaction inhibitor with its target on the water splitting enzyme located in PSII. In the search for new herbicides from natural compounds, flavonoids 1 and 2 and flavonoid analogues quercetin (3), apigenin (4), genistein (5), and eupatorin (6) were assessed for their effect in vitro on the photosynthetic electron transport chain and in vivo on the germination and growth of the plants Physalis ixocarpa, Trifolium alexandrinum and Lolium perenne. Flavonoid 3 was the most active inhibitor of the photosynthetic uncoupled electron flow (I50 = 114 µM) with a lower log P value (1.37). Results in vivo suggest that 1, 2, 3, and 5 behave as pre- and postemergent herbicides, with 3 and 5 being more active.