Correction: Abbas et al. Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies. Antioxidants 2022, 11, 1160.

In the original publication [...].

Dryopteris juxtapostia Root and Shoot: Determination of Phytochemicals; Antioxidant, Anti-Inflammatory, and Hepatoprotective Effects; and Toxicity Assessment.

An estimated 450 species of Dryopteris in the Dryoperidaceae family grow in Japan, North and South Korea, China, Pakistan, and Kashmir. This genus has been reported to have biological capabilities; however, research has been conducted on Dryopteris juxtapostia. Therefore, with the present study, we aimed to exploring the biological potential of D. juxtapostia root and shoot extracts. We extracted dichloromethane and methanol separately from the roots and shoots of D. juxtapostia. Antioxidant activity was determined using DPPH, FRAP, and H2O2 assays, and anti-inflammatory activities were evaluated using both in vitro (antiurease activity) and in vivo (carrageenan- and formaldehyde-induced paw edema) studies. Toxicity was evaluated by adopting a brine shrimp lethality assay followed by determination of cytotoxic activity using an MTT assay. Hepatoprotective effects of active crude extracts were examined in rats. Activity-bearing compounds were tentatively identified using LC-ESI-MS/MS analysis. Results suggested that D. juxtapostia root dichloromethane extract exhibited better antioxidant (DPPH, IC50 of 42.0 µg/mL; FRAP, 46.2 mmol/g; H2O2, 71% inhibition), anti-inflammatory (urease inhibition, 56.7% at 50 µg/mL; carrageenan-induced edema inhibition, 61.7% at 200 µg/mL; formaldehyde-induced edema inhibition, 67.3% at 200 µg/mL), brine shrimp % mortality (100% at 1000 µg/mL), and cytotoxic (HeLa cancer, IC50 of 17.1 µg/mL; prostate cancer (PC3), IC50 of 45.2 µg/mL) effects than D. juxtapostia root methanol extract. D. juxtapostia shoot dichloromethane and methanol extracts exhibited non-influential activity in all biological assays and were not selected for hepatoprotective study. D. juxtapostia root methanol extract showed improvement in hepatic cell structure and low cellular infiltration but, in contrast the dichloromethane extract, did not show any significant improvement in hepatocyte morphology, cellular infiltration, or necrosis of hepatocytes in comparison to the positive control, i.e., paracetamol. LC-ESI-MS/MS analysis showed the presence of albaspidin PP, 3-methylbutyryl-phloroglucinol, flavaspidic acid AB and BB, filixic acid ABA and ABB, tris-desaspidin BBB, tris-paraaspidin BBB, tetra-flavaspidic BBBB, tetra-albaspidin BBBB, and kaempferol-3-O-glucoside in the dichloromethane extract, whereas kaempferol, catechin, epicatechin, quinic acid, liquitrigenin, and quercetin 7-O-galactoside in were detected in the methanol extract, along with all the compounds detected in the dichloromethane extract. Hence, D. juxtapostia is safe, alongside other species of this genus, although detailed safety assessment of each isolated compound is obligatory during drug discovery.

Bioactive Compounds, Antioxidant, Anti-Inflammatory, Anti-Cancer, and Toxicity Assessment of Tribulus terrestris-In Vitro and In Vivo Studies.

Tribulus terrestris L. belongs to the family Zygophyllaceae and integral part of various ancient medicinal systems including Chinese, Indian, and European to combat various health ailments. The aim of the present study was to assess the phytochemical constituents, in vitro antioxidant activity using DPPH, FRAP, and H2O2 assays, in vitro anticancer activity using MTT assay, and in vitro and in vivo anti-inflammatory properties of T. terrestris. The acute and sub-acute toxicity of extracts exhibiting most biological potential was examined using murine models. Liquid-liquid partitioning followed by RP-HPLC sub-fraction of crude extract was performed. After that, ESI-MS/MS analysis was done for the timid identification of bioactive metabolites responsible for bioactivities of sub-fractions and HPLC analysis to quantify the compounds using external standards. Among all extracts, T. terrestris methanol extract was noted to hold maximum phenolic (341.3 mg GAE/g) and flavonoid (209 mg QE/g) contents, antioxidant activity in DPPH (IC50 71.4 µg/mL), FRAP (35.3 mmol/g), and H2O2 (65.3% inhibition) assays, anti-inflammatory activities in vitro at 400 µg/mL (heat-induced hemolysis, % inhibition 68.5; egg albumin denaturation, % inhibition 75.6%; serum albumin denaturation, % inhibition 80.2), and in vivo at 200 mg/kg (carrageenan-induced paw edema, % inhibition 69.3%; formaldehyde-induced paw edema, % inhibition 71.3%) and anticancer activity against breast cancer cell (MCF-7) proliferation (IC50 74.1 µg/mL). Acute and sub-acute toxicity studies recorded with no change in body weight, behavior, hematological, serum, and histopathological parameters in treated rats with T. terrestris methanol extracts when compared to control group. Fraction B obtained through liquid-liquid partitioning resulted in more bioactive potential as compared to the parent methanol extract. RP-HPLC analysis of fraction B resulted with four sub-fractions (TBTMF1-TBTMF4), wherein TBTMF3 delineated notable bioactive capabilities as compared to other fractions and parent methanol extract. ESI-MS/MS analysis of TBTMF3 resulted with tentative identification of myricetin, rutin, liquitrigenin, physcion, and protodioscin. It can be stated that T. terrestris is a potential bearing herb and findings of current study further verify the claims made in ancient medicinal systems. However, after investigation of each identified compound, it must be considered for drug discovery.

Phytochemical Profile, Biological Properties, and Food Applications of the Medicinal Plant Syzygium cumini.

Syzygium cumini, locally known as Jamun in Asia, is a fruit-bearing crop belonging to the Myrtaceae family. This study aims to summarize the most recent literature related to botany, traditional applications, phytochemical ingredients, pharmacological activities, nutrition, and potential food applications of S. cumini. Traditionally, S. cumini has been utilized to combat diabetes and dysentery, and it is given to females with a history of abortions. Anatomical parts of S. cumini exhibit therapeutic potentials including antioxidant, anti-inflammatory, analgesic, antipyretic, antimalarial, anticancer, and antidiabetic activities attributed to the presence of various primary and secondary metabolites such as carbohydrates, proteins, amino acids, alkaloids, flavonoids (i.e., quercetin, myricetin, kaempferol), phenolic acids (gallic acid, caffeic acid, ellagic acid) and anthocyanins (delphinidin-3,5-O-diglucoside, petunidin-3,5-O-diglucoside, malvidin-3,5-O-diglucoside). Different fruit parts of S. cumini have been employed to enhance the nutritional and overall quality of jams, jellies, wines, and fermented products. Today, S. cumini is also used in edible films. So, we believe that S. cumini's anatomical parts, extracts, and isolated compounds can be used in the food industry with applications in food packaging and as food additives. Future research should focus on the isolation and purification of compounds from S. cumini to treat various disorders. More importantly, clinical trials are required to develop low-cost medications with a low therapeutic index.

Syzygium cumini (L.) Skeels extracts; in vivo anti-nociceptive, anti-inflammatory, acute and subacute toxicity assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels has been extensively used in the ancient medical system of Pakistan, India, Bangladesh, and Sri Lanka to combat diabetes, inflammation, and renal disorders. These health-promoting aspects of S. cumini are related to bioactive metabolites such as phenolic acids, anthocyanins, tannins, and flavonoids. AIM OF THE STUDY: Earlier to this study, we have reported S. cumini extracts as potential sources of bioactive compounds bearing antioxidant and anti-inflammatory properties. However, prior further suggesting S. cumini fruit extracts for consumption against inflammatory disorders, it was mandatory to validate the claim and explore toxicity of the extracts. This study aims to determine the in vivo anti-nociceptive, anti-inflammatory, acute, and subacute toxicity properties of S. cumini crude extracts, followed by identifying and quantifying bioactive metabolites. MATERIAL AND METHODS: In the present study, the anti-nociceptive and anti-inflammatory potential of S. cumini sequential crude extracts were evaluated using formalin and glutamate-induced paw licking method in mice. The acute and sub-acute toxicity assessment of active extract was performed by oral administration in rats. An acute toxicity trial was performed with two different doses, i.e., 2000 mg/kg and 3000 mg/kg for consecutive 14 days, whereas a sub-acute toxicity study was conducted at doses of 750 mg/kg and 1500 mg/kg for the next 28 days. Identification of bioactive compounds was performed using HPLC, and at the end, in silico docking calculations of identified compounds were performed. RESULTS: The 100% methanolic extract (SCME) protected the mice from painful stimulation of formalin and glutamate in a dose-dependent manner with the maximum effect of 49% and 67% at 200 mg/kg, respectively, followed by moderate and non-influential effects of 50% methanolic extract and dichloromethane (DCM) extracts when compared to control, i.e., normal saline. The results of acute toxicity recorded LD50 of SCME over 3000 mg/kg, and no antagonistic effects were recorded during the subacute study when SCME dispensed at the rate of 750 mg/kg and 1500 mg/kg. SCME was found to induce no adverse effects to kidney, heart, liver, spleen, and paired lungs examined by hematological, serum biochemical, histological analysis. HPLC analysis of S. cumini 100% methanolic extracts revealed the presence of delphinidin 3-glucoside, peonidin-3,5-diglucoside, scopoletin, and umbelliferone at the concentration of 127.4, 2104, 31.3, 10.4 µg/g whereas in 50% methanolic extract, the quinic acid, catechin, and myricetin were present at the concentration of 54.9, 63.7, 12.3 µg/g, respectively. Umbelliferone and scopoletin are newly reported compounds in the present study. In silico docking calculations of these compounds indicated the potential of anti-nociceptive and anti-inflammatory activities. CONCLUSIONS: These findings validate that S. cumini fruit extracts are a rich source of bioactive compounds that needs to be considered to enhance biological activities with lesser side effects.

Antioxidant and Anti-Inflammatory Effects of Peganum harmala Extracts: An In Vitro and In Vivo Study.

Peganum harmala (P. harmala) belongs to the family Zygophyllaceae, and is utilized in the traditional medicinal systems of Pakistan, China, Morocco, Algeria, and Spain to treat several chronic health disorders. The aim of the present study was to identify the chemical constituents and to evaluate the antioxidant, anti-inflammatory, and toxicity effects of P. harmala extracts both in vitro and in vivo. Sequential crude extracts including 100% dichloromethane, 100% methanol, and 70% aqueous methanol were obtained and their antioxidant and anti-inflammatory effects evaluated both in vitro and in vivo. The anti-inflammatory effect of the extract was investigated using the carrageenan-induced paw edema method in mice, whereas the toxicity of the most active extract was evaluated using an acute and subacute toxicity rat model. In addition, we have used the bioassay-guided approach to obtain potent fractions, using solvent-solvent partitioning and reversed phase high performance liquid chromatography from active crude extracts; identification and quantification of compounds from the active fractions was achieved using electrospray ionization mass spectrometry and high performance liquid chromatography techniques. Results revealed that the 100% methanol extract of P. harmala exhibits significant in vitro antioxidant activity in DPPH assay with an IC50 of 49 µg/mL as compared to the standard quercetin with an IC50 of 25.4 µg/mL. The same extract exhibited 63.0% inhibition against serum albumin denaturation as compared to 97% inhibition by the standard diclofenac sodium in an in vitro anti-inflammatory assay, and in vivo anti-inflammatory against carrageenan-induced paw edema (75.14% inhibition) as compared to 86.1% inhibition caused by the standard indomethacin. Furthermore, this extract was not toxic during a 14 day trial of acute toxicity when given at a dose of 3 g/kg, indicating that the lethal dose (LD50) of P. harmala methanol extract was greater than 3 g/kg. P. harmala methanolic fraction 2 obtained using bioassay-guided fractionation showed the presence of quinic acid, peganine, harmol, harmaline, and harmine, confirmed by electrospray ionization mass spectrometry and quantified using external standards on high performance liquid chromatography. Taken all together, the current investigation further confirms the antioxidant, anti-inflammatory, and safety aspects of P. harmala, which justifies its use in folk medicine.