Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat: In vitro and in vivo studies.

Objective: To assess acute toxicity, the in vitro and in vivo effects of methanol and ethyl acetate extracts (JME and JEE) of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes. Methods: Acute toxicity of JME and JEE was determined using Lorke's method. In vitro and in vivo opening of the mitochondrial membrane permeability transition pore (MMPT pore) was spectrophotometrically assayed. Production of malondialdehyde (MDA) as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase (ALP), aspartate and alanine aminotransferase (AST and ALT) and gamma-glutamyl transferase (GGT) was also investigated. Results: JME had an LD50 of 3 808 mg/kg b.w whereas JEE had an LD50 greater than 5 000 mg/kg b.w. of rats. After the rats have been fed with both extracts, a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity. From the in vitro and in vivo studies, both extracts prompted intact mitochondria to open their MMPT pores. When compared to the control, lipid peroxide product release and ATPase activity were significantly increased (P < 0.05) in vitro and in vivo. The activities of AST, ALT, and GGT were all reduced at 50 mg/kg when treated with JME, but the activity of AST was considerably enhanced when treated with JEE (P < 0.05). The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity, profound MMPTpore induction, and enhanced ATPase activity, but an increased MDA production. Conclusion: Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis, however, further studies are needed to better clarify the molecular mechanism involved in these phenomena.

Analysis of Pyrrolizidine Alkaloids in Stingless Bee Honey and Identification of a Botanical Source as Ageratum conyzoides.

Stingless bee honeys (SBHs) from Australian and Malaysian species were analysed using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the presence of pyrrolizidine alkaloids (PAs) and the corresponding N-oxides (PANOs) due to the potential for such hepatotoxic alkaloids to contaminate honey as a result of bees foraging on plants containing these alkaloids. Low levels of alkaloids were found in these SBHs when assessed against certified PA standards in targeted analysis. However, certain isomers were identified using untargeted analysis in a subset of honeys of Heterotrigona itama which resulted in the identification of a PA weed species (Ageratum conyzoides) near the hives. The evaluation of this weed provided a PA profile matching that of the SBH of H. itama produced nearby, and included supinine, supinine N-oxide (or isomers) and acetylated derivatives. These PAs lacking a hydroxyl group at C7 are thought to be less hepatoxic. However, high levels were also observed in SBH (and in A. conyzoides) of a potentially more toxic diester PA corresponding to an echimidine isomer. Intermedine, the C7 hydroxy equivalent of supinine, was also observed. Species differences in nectar collection were evident as the same alkaloids were not identified in SBH of G. thoracica from the same location. This study highlights that not all PAs and PANOs are identified using available standards in targeted analyses and confirms the need for producers of all types of honey to be aware of nearby potential PA sources, particularly weeds.

Synthesis of Extract-Bacterial Cellulose Composite Using Ageratum conyzoides L. and Chromolaena odorata L., Its Antibacterial Activities, and Biodegradability Properties.

Bacterial cellulose is a natural polymer produced by fermentation of coconut water using Acetobacter xylinum bacteria. This study aimed to synthesize a novel composite of bacterial cellulose impregnated with plant extracts that had an antibacterial activity that have the potential to be used as a food packaging material to maintain food quality. Pure bacterial cellulose (pure BC) was impregnated using Ageratum conyzoides L. leaf extract (AC-BC) and Chromolaena odorata L. leaf extract (CO-BC), which contain secondary metabolites with potential as antibacterial. The study began with the synthesis of pure BC, AC-BC, and CO-BC composites then characterized by SEM-EDX and FTIR, continued with antibacterial activity tests against S. aureus, S. typhimurium, E. coli, and their biodegradability tests. The results of SEM and FTIR characterization showed the success of the impregnation process for antibacterial compounds. The results of the antibacterial activity of AC-BC disc diffusion against S. typhimurium and E. coli showed good antibacterial activity of 9.82 mm and 8.41 mm, respectively. The similar result showed with the antibacterial activity of CO-BC disc diffusion against S. typhimurium and E. coli that showed good activity of 9.73 mm and 6.82 mm, respectively. On the other hand, the biodegradability test showed that the impregnation of bacterial cellulose slowed down the degradation process in the soil. This study confirmed the potential application of bacterial cellulose-plant extracts as an active and biodegradable food packaging.

Molecular Signature of a Novel Alternanthera Yellow Vein Virus Variant Infecting the Ageratum conyzoides Weed in Oman.

Alternanthera yellow vein virus (AlYVV), a monopartite begomovirus, has been identified infecting a diverse range of crops and native plants in Pakistan, India, and China. However, distinctive yellow vein symptoms, characteristic of begomovirus infection, were observed on the Ageratum conyzoides weed in Oman, prompting a thorough genomic characterization in this study. The results unveiled a complete genome sequence of 2745 base pairs and an associated betasatellite spanning 1345 base pairs. In addition, Sequence Demarcation Tool analyses indicated the highest nucleotide identity of 92.8% with a previously reported AlYVV-[IN_abalpur_A_17:LC316182] strain, whereas the betasatellite exhibited a 99.8% nucleotide identity with isolates of tomato leaf curl betasatellite. Thus, our findings propose a novel AlYVV Oman virus (AlYVV-OM) variant, emphasizing the need for additional epidemiological surveillance to understand its prevalence and significance in Oman and the broader region. To effectively manage the spread of AlYVV-OM and minimize its potential harm to (agro)ecosystems, future research should focus on elucidating the genetic diversity of AlYVV-OM and its interactions with other begomoviruses.

The Potentials of Ageratum conyzoides and Other Plants from Asteraceae as an Antiplasmodial and Insecticidal for Malaria Vector: An Article Review.

Background: Malaria is a life-threatening disease prevalent in tropical and subtropical regions. Artemisinin combination therapy (ACT) used as an antimalarial treatment has reduced efficacy due to resistance, not only to the parasite but also to the vector. Therefore, it is important to find alternatives to overcome malaria cases through medicinal plants such as Ageratum conyzoides and other related plants within Asteraceae family. Purpose: This review summarizes the antimalarial and insecticidal activities of A. conyzoides and other plants belonging to Asteraceae family. Data Source: Google Scholar, PubMed, Science Direct, and Springer link. Study Selection: Online databases were used to retrieve journals using specific keywords combined with Boolean operators. The inclusion criteria were articles with experimental studies either in vivo or in vitro, in English or Indonesian, published after 1st January 2000, and full text available for inclusion in this review. Data Extraction: The antimalarial activity, insecticidal activity, and structure of the isolated compounds were retrieved from the selected studies. Data Synthesis: Antimalarial in vitro study showed that the dichloromethane extract was the most widely studied with an IC50 value <10 µg/mL. Among 84 isolated active compounds, 2-hydroxymethyl-non-3-ynoic acid 2-[2,2']-bithiophenyl-5- ethyl ester, a bithienyl compound from the Tagetes erecta plant show the smallest IC50 with value 0.01 and 0.02 µg/mL in Plasmodium falciparum MRC-pf-2 and MRC-pf-56, respectively. In vivo studies showed that the aqueous extract of A. conyzoides showed the best activity, with a 98.8% inhibition percentage using a 100 mg/kg dose of Plasmodium berghei (NK65 Strain). (Z)- γ-Bisabolene from Galinsoga parviflora showed very good insecticidal activity against Anopheles stephensi and Anopheles subpictus with LC50 values of 2.04 µg/mL and 4.05 µg/mL. Conclusion: A. conyzoides and other plants of Asteraceae family are promising reservoirs of natural compounds that exert antimalarial or insecticidal activity.

Modeling Study of the Effects of Ageratum conyzoides on the Transmission and Control of Citrus Huanglongbing.

Ageratum conyzoides (A. conyzoides) is commonly found or intentionally planted in citrus orchards due to its ability to provide habitat and breeding grounds for the natural enemies of citrus pests. This study aims to expand from a switching Huanglongbing model by incorporating the effects of A. conyzoides, vector preferences for settling, and pesticide application intervals on disease transmission. Additionally, we establish the basic reproduction number R0 and its calculation for a general switching compartmental epidemic model. Theoretical findings demonstrate that the basic reproduction number serves as a threshold parameter to characterize the dynamics of the models: if R0<1, the disease will disappear, whereas if R0>1, it will spread. Numerical results indicate that the recruitment rate of A. conyzoides not only affects the spread speed of Huanglongbing but also leads to paradoxical effects. Specifically, in cases of high infection rates, a low recruitment rate of A. conyzoides can result in a decrease, rather than an increase, in the basic reproduction number. Conversely, a high recruitment rate can accelerate the spread of Huanglongbing. Furthermore, we show how different vector bias and pesticide spraying periods affect the basic reproduction number.

Bio-oil and biochar production from Ageratum conyzoides using triple-stage hydrothermal liquefaction and utilization of biochar in removal of multiple heavy metals from water.

Production of low-cost biomass and its utilization for producing cost effective and eco-friendly bioenergy as well as for removing heavy metals from water can be explored as an approach to meet the sustainable development goals. In light of the above-mentioned study, hydrothermal liquefaction (HTL) of Billy goat weed (BGW; Ageratum conyzoides) was carried out to produce bio-oil. In addition, the residual biochar from the HTL process was activated to obtain Act-BC and was further modified to produce MnO2-loaded biochar (Act-BC@MnO2-25%). The HTL of BGW was done at three different temperatures, i.e., 250 °C, 350 °C and 450 °C in a high-pressure batch reactor to maximize the bio-oil yield. Also, two different HTL methods i.e., single-stage HTL and triple-stage HTL of BGW were compared and discussed in detail. The bio-oil obtained via the triple-stage HTL was rich in carbon, hydrogen, and nitrogen. It also showed a higher heating value (HHV) and bio-oil yield (46%) than the single-stage. The residual biochar obtained at 450 °C (Act-BC) and MnO2 modified (Act-BC@MnO2-25%) were then tested to adsorb multiple heavy metal (i.e., Pb(II), Cd(II), Cu(II), and Ni(II)) from water. The kinetics data obtained from the adsorption experiment with Act-BC@MnO2-25% were well fitted to PSO kinetics model. The isotherm data were well aligned with the Langmuir model; the adsorption capacity of Act-BC@MnO2-25% was estimated to be 198.70 ± 11.40 mg g-1, 93.70 ± 6.60 mg g-1, 78.90 ± 7.20 mg g-1 and 30.50 ± 2.10 mg g-1 for Pb(II), Cd(II), Cu(II), and Ni(II), respectively. Furthermore, Act-BC@MnO2-25% remained active for metal ions absorption even after six consecutive uses. The result obtained from this study clearly demonstrates that the triple-stage HTL of BGW is a promising technology to achieve both remediation of metal-contaminated water and production of bioenergy.

First report of Capsicum chlorosis virus naturally infecting Ageratum conyzoides in China.

Capsicum chlorosis virus (CaCV; family Tospoviridae, genus Orthotospovirus) was first reported to infect capsicum (Capsicum annuum) and tomato (Solanum lycopersicum) in Australia in 2002 (McMichael et al., 2002). Subsequently, its infection was detected in different plants including waxflower (Hoya calycina Schlecter) in the United States (Melzer et al. 2014), peanut (Arachis hypogaea) in India (Vijayalakshmi et al. 2016), and spider lily (Hymenocallis americana) (Huang et al. 2017), Chilli pepper (Capsicum annuum) (Zheng et al. 2020), and Feiji cao (Chromolaena odorata) (Chen et al. 2022) in China. Ageratum conyzoides L. (commonly known as goat weed, family Asteraceae) is a natural weed in crop fields distributed in subtropical and tropical areas and a reservoir host of numerous plant pathogens (She et al. 2013). In April 2022, we observed that 90% of plants of A. conyzoides in maize fields in Sanya, Hainan province, China, exhibited typical virus-like symptoms of vein yellowing, leaf chlorosis, and distortion (Fig. S1 A-C). Total RNA was extracted from one symptomatic leaf of A. conyzoides. Small RNA libraries were constructed using the small RNA Sample Pre Kit (Illumina, San Diego, USA) for sequencing with an Illumina Novaseq 6000 platform (Biomarker Technologies Corporation, Beijing, China). A total 15,848,189 clean reads were obtained after removing low-quality reads. Quality-controlled qualified reads were assembled into contigs using Velvet 1.0.5 software with a k-mer value of 17. One hundred contigs shared nucleotide identity ranging from 85.7% to 100% with the CaCV using BLASTn searches online (https://blast.ncbi.nlm.nih.gov/Blast.cgi?). Numerous contigs (45, 34, and 21) obtained in this study were mapped to the L, M, and S RNA segments of the CaCV-Hainan isolate (GenBank accession no. KX078565- KX078567) from spider lily (Hymenocallis americana) in Hainan province, China, respectively. The full-length of L, M, and S RNA segments of CaCV-AC were determined to be 8,913, 4,841, and 3,629 bp, respectively (GenBank accession no. OQ597167- OQ597169). Furthermore, five symptomatic leaf samples were tested to be positive for CaCV using a CaCV enzyme-linked immunosorbent assay (ELISA) kit (MEIMIAN, Jiangsu, China) (Fig. S1-D). Total RNA from these leaves was amplified by RT-PCR with two sets of primer pairs. Primers CaCV-F (5'-ACTTTCCATCAACCTCTGT-3') and CaCV-R (5'-GTTATGGCCATATTTCCCT-3') were used for the amplification of 828 bp fragment from nucleocapsid protein (NP) on CaCV S RNA. While another, primers gL3637 (5'-CCTTTAACAGTDGAAACAT-3') and gL4435c (5'-CATDGCRCAAGARTGRTARACAGA-3') were used for the amplification of 816 bp fragment from RNA-dependent RNA polymerase (RdRP) on CaCV L RNA (Fig. S1-E and -F) (Basavaraj et al. 2020). These amplicons were cloned into the pCE2 TA/Blunt-Zero vector (Vazyme, Nanjing, China) and three independent positive colonies of Escherichia coli DH5α carrying each viral amplicon were sequenced. These sequences were deposited in the GenBank database under accession nos. OP616700-OP616709. Pairwise sequence comparison revealed that nucleotide sequences of NP and RdRP genes of the five CaCV isolates shared 99.5% (812 bp out of 828 bp) and 99.4% (799 bp out of 816 bp) nucleotide identities, respectively. They showed 86.2-99.2% and 86.5-99.1% nucleotide identities with corresponding nucleotide sequences of other CaCV isolates derived from GenBank database, respectively. The highest nucleotide sequence identity (99%) of the CaCV isolates obtained in the study was observed with the CaCV-Hainan isolate. Phylogenetic analysis based on NP amino acid demonstrated that six CaCV isolates (this study = 5 and NCBI database = 1) clustered into one distinct clade (Fig. S2). Our data confirmed for the first time the presence of CaCV naturally infecting A. conyzoides plant in China, which enriches information on the host range and will be helpful for disease management.

One-Pot Synthesis of Silver Nanoparticles Derived from Aqueous Leaf Extract of Ageratum conyzoides and Their Biological Efficacy.

The main objective of the present research work is to assess the biological properties of the aqueous plant extract (ACAE) synthesised silver nanoparticles from the herbal plant Ageratum conyzoides, and their biological applications. The silver nanoparticle syntheses from Ageratum conyzoides (Ac-AgNPs) were optimised with different parameters, such as pH (2, 4, 6, 8 and 10) and varied silver nitrate concentration (1 mM and 5 mM). Based on the UV-vis spectroscopy analysis of the synthesised silver nanoparticles, the concentration of 5 mM with the pH at 8 was recorded as the peak reduction at 400 nm; and these conditions were optimized were used for further studies. The results of the FE-SEM analysis recorded the size ranges (~30-90 nm), and irregular spherical and triangular shapes of the AC-AgNPs were captured. The characterization reports of the HR-TEM investigation of AC-AgNPs were also in line with the FE-SEM studies. The antibacterial efficacies of AC-AgNPs have revealed the maximum zone of inhibition against S. typhi to be within 20 mm. The in vitro antiplasmodial activity of AC-AgNPs is shown to have an effective antiplasmodial property (IC50:17.65 µg/mL), whereas AgNO3 has shown a minimum level of IC50: value 68.03 µg/mL, and the Ac-AE showed >100 µg/mL at 24 h of parasitaemia suppression. The α-amylase inhibitory properties of AC-AgNPs have revealed a maximum inhibition similar to the control Acarbose (IC50: 10.87 µg/mL). The antioxidant activity of the AC-AgNPs have revealed a better property (87.86% ± 0.56, 85.95% ± 1.02 and 90.11 ± 0.29%) when compared with the Ac-AE and standard in all the three different tests, such as DPPH, FRAP and H2O2 scavenging assay, respectively. The current research work might be a baseline for the future drug expansion process in the area of nano-drug design, and its applications also has a lot of economic viability and is a safer method in synthesising or producing silver nanoparticles.

The aqueous extracts of Ageratum conyzoides inhibit inflammation by suppressing NLRP3 inflammasome activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ageratum conyzoides L. (Asteraceae), a well-known and widely distributed traditional tropical medicinal herb, has been used to treat diverse diseases. Our preliminary research has shown that aqueous extracts of A. conyzoides leaf (EAC) have anti-inflammatory activity. However, the detailed underlying anti-inflammatory mechanism of EAC is still unclear. AIM OF THE STUDY: To determine the anti-inflammatory mechanism of action of EAC. MATERIALS AND METHODS: The major constituents of EAC were identified by ultra-performance liquid chromatography (UPLC) combined with quadrupole-time-of-flight mass/mass spectrometry (UPLC-Q-TOF-MS/MS). LPS and ATP were used to activate the NLRP3 inflammasome in two types of macrophages (RAW 264.7 and THP-1 cells). The cytotoxicity of EAC was measured by the CCK8 assay. The levels of inflammatory cytokines and NLRP3 inflammasome-related proteins were detected by ELISA and western blotting (WB), respectively. The oligomerization of NLRP3 and ASC and the resulting inflammasome complex formation were observed by immunofluorescence. The intracellular reactive oxygen species (ROS) level was measured by flow cytometry. Finally, an MSU-induced peritonitis model was established to evaluate the anti-inflammatory effects of EAC in vivo. RESULTS: Twenty constituents were identified in the EAC. Kaempferol 3,7-diglucoside, 1,3,5-tricaffeoylquinic acid, and kaempferol 3,7,4'-triglucoside were found to be the most potent ingredients. EAC significantly reduced the levels of IL-1ß, IL-18, TNF-α, and caspase-1 in the two types of activated macrophages, implying that EAC can inhibit the activation of the NLRP3 inflammasome. A mechanistic study revealed that EAC inhibited NLRP3 inflammasome activation by blocking NF-κB signalling pathway activation and scavenging the level of intracellular ROS to prevent NLRP3 inflammasome assembly in macrophages. Furthermore, EAC attenuated the in vivo expression of inflammatory cytokines by suppressing NLRP3 inflammasome activation in a peritonitis mouse model. CONCLUSION: Our results demonstrated that EAC inhibited inflammation by suppressing NLRP3 inflammasome activation, highlighting that this traditional herbal medicine might be used to treat NLRP3 inflammasome-driven inflammatory diseases.

Green Biosynthesis of Silver Nanoparticles Using Aqueous Extracts of Ageratum Conyzoides and Their Anti-Inflammatory Effects.

The NLRP3 inflammasome, which plays a central role in innate immunity, is linked to a variety of inflammatory diseases, and thus it may provide a new target for the treatment of those diseases. Biosynthesized silver nanoparticles (AgNPs), particularly those synthesized using medicinal plant extracts, have recently been shown to be a promising therapeutic option. Herein, the aqueous extract of Ageratum conyzoids was used to prepare a series of sized AgNPs (AC-AgNPs), in which the smallest mean particle size was 30 ± 1.3 nm with a polydispersity of 0.328 ± 0.009. The ζ potential value was -28.77 with a mobility of -1.95 ± 0.24 cm2/(v·s). Its main ingredient, elemental silver, accounted for about 32.71 ± 4.87% of its mass, and other ingredients included amentoflavone-7,7⁗-dimethyl ether, 1,3,5-tricaffeoylquinic acid, kaempferol 3,7,4'-triglucoside, 5,6,7,3',4',5'-hexamethoxyflavone, kaempferol, and ageconyflavone B. In LPS+ATP-stimulated RAW 264.7 and THP-1 cells, AC-AgNPs significantly inhibited the release of IL-1ß, IL-18, TNF-α, and caspase-1, indicating that AC-AgNPs can inhibit the activation of the NLRP3 inflammasome. The mechanistic study revealed that AC-AgNPs could decrease the phosphorylation levels of IκB-α and p65, resulting in decreased expression of NLRP3 inflammasome-related proteins, including pro-IL-1ß, IL-1ß, procaspase 1, caspase 1P20, NLRP3, and ASC, and also scavenge the level of intracellular ROS to prevent NLRP3 inflammasome assembly. Furthermore, AC-AgNPs attenuated the in vivo expression of inflammatory cytokines by suppressing NLRP3 inflammasome activation in a peritonitis mouse model. Our study provides evidence that the as-prepared AC-AgNPs can inhibit the inflammatory process by suppressing NLRP3 inflammasome activation and might be used to treat NLRP3 inflammasome-driven inflammatory diseases.

Therapeutic effects of aqueous extract of bioactive active component of Ageratum conyzoides on the ovarian-uterine and hypophysis-gonadal axis in rat with polycystic ovary syndrome: Histomorphometric evaluation and biochemical assessment.

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder, affecting women of reproductive age. Ageratum conyzoïdes (AGC) is used traditionally in the treatment of fever, rheumatism, and ulcer. This study investigates the effects of AGC on ovarian-uterine in PCOS rats. Methods: Female rats were randomized into four groups (n = 6). Group A control received 2 ml distilled water. Group B received a single dose of 4 mg/kg body weight (bwt) i.p estradiol valerate (EV). Group C received 500 mg/kg bwt AGC and group D received a single dose of 4 mg/kg bwt i.p EV followed by 500 mg/kg bwt AGC orally for 30 days. Parameters tested include follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), estradiol (E2), progesterone (P), C-reactive protein (CRP), interleukin (IL)-6, IL-18 and tumor necrosis factor (TNF)- α, malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), total protein (TP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and ovary and uterus histomorphometric. Results: Ageratum conyzoides decrease insulin resistance, obesity indices, TC, TG, LDL, MDA, T, LH, FSH, CRP, IL-6, IL-18, and TNF- α in PCOS rats. And increase HDL, E2, P, TP, CAT, and SOD in PCOS rats. AGC improved ovary and uterus histo-architecture, tertiary, and Graafian follicles, corpus luteum and endometrial thickness increased,and cystic and atretic follicles decreased. Conclusion: Ageratum conyzoides improved insulin sensitivity, antioxidant activities, hormonal imbalance, inflammatory makers, and histological changes in PCOS rats. Therefore AGC can be used as a potential adjuvant agent in the treatment of PCOS.

Turning Waste into Beneficial Resource: Implication of Ageratum conyzoides L. in Sustainable Agriculture, Environment and Biopharma Sectors.

The annual herb, Ageratum conyzoides L. (Asteraceae), is distributed throughout the world. Although invasive, it can be very useful as a source of essential oils, pharmaceuticals, biopesticides, and bioenergy. However, very limited information exists on the molecular basis of its different utility as previous investigations were mainly focused on phytochemical/biological activity profiling. Here we have explored various properties of A. conyzoides that may offer environmental, ecological, agricultural, and health benefits. As this aromatic plant harbors many important secondary metabolites that may have various implications, biotechnological interventions such as genomics, metabolomics and tissue-culture can be indispensable tools for their mass-production. Further, A. conyzoides acts as a natural reservoir of begomoviruses affecting a wide range of plant species. As the mechanisms of disease spreading and crop infection are not fully clear, whole-genome sequencing and various advanced molecular technologies including RNAi, CRISPER/Cas9, multi-omics approaches, etc., may aid to decipher the molecular mechanism of such disease development and thus, can be useful in crop protection. Overall, improved knowledge of A. conyzoides is not only essential for developing sustainable weed control strategy but can also offer potential ways for biomedicinal, environment, safe and clean agriculture applications.

Wound Healing Effectivity of the Ethanolic Extracts of Ageratum conyzoides L. Leaf (White and Purple Flower Type) and Centella asiatica and Astaxanthin Combination Gel Preparation in Animal Model

The study's objective was to determine the wound healing activity of the combination of ethanolic extracts of Ageratum conyzoides L. leaf (white and purple), Centella asiatica, and astaxanthin gel preparation. Materials and Methods: For in-gel preparation, three different formulas of gelling agents, namely carbopol 934 (1%), hydroxypropyl methylcellulose (HPMC) (9%), and natirum-carboxymethylcellulose (Na-CMC) (4%), were employed. Then, the organoleptic, pH, spreadability, and viscosity of the formulas were evaluated. To determine wound healing activity, six treatments, including negative control (placebo), positive control (bioplacenton), BP5 (A. conyzoides L. leaf ethanolic extract of white flower type 5%, C. asiatica L. Urb leaf ethanolic extract 2.5%, astaxanthin 0.05%), BU5 (A. conyzoides L. leaf ethanolic extract of purple flower type 5%, C. asiatica L. Urb leaf ethanolic extract 2.5%, astaxanthin 0.05%), BU10 (A. conyzoides L. leaf ethanolic extract of purple flower type 10%, C. asiatica L. Urb leaf ethanolic extract 5%, and astaxanthin 0.1%), and BP10 (A. conyzoides L. leaf ethanolic extract of white flower type 10%, C. asiatica L. Urb leaf ethanolic extract 5%, and astaxanthin 0.1%) were evaluated. All treatments were applied to an incision wound (1.5 cm). Measurement of the wound length was conducted daily for 14 days. Results: The results showed that the carbopol 934 (1%) gelling agent formula was better than HPMC and Na-CMC. Meanwhile, the percentages of wound healing activity for negative, positive, BP5, BU5, BU10, and BP10 groups were 72.51%, 69.36%, 70.14%, 81.70%, 86.54%, and 80.21%, respectively. The BU5 and BU10 showed significant activity (p<0.05) compared with positive and negative controls. Conclusion: BU10 provided the best wound healing activity and can be developed as a commercial product.

Potential of Ageratum conyzoides in Inhibiting Nitric Oxide Synthase.

<b>Background and Objective:</b> Inflammation occurs <i>via</i> several mechanisms, one of which includes the production of Nitric Oxide (NO) catalyzed by inducible nitric oxide synthase (iNOS), which is inhibited selectively by isothioureas. <i>Ageratum conyzoides</i> L. has shown activity in reducing pain and inflammation, although the molecular mechanism had not been undertaken. The objectives of this work were (1) to study the mechanism of anti-inflammatory activity of <i>A. conyzoides</i> through inhibition of iNOS, (2) to correlate the iNOS inhibitory activity of the plant with the total flavonoid content of the plants and (3) to identify the flavonol synthase (FLS), an enzyme that catalyzes the production of quercetin. <b>Materials and Methods:</b> The inhibitory activity against iNOS was assayed by <i>in vitro</i> method. The total flavonoids (calculated as quercetin) of <i>A. conyzoides</i> were determined by fluorometry. The protein extraction of the leaves was carried out by employing Laing and Christeller's (2004) method, followed with SDS-PAGE. <b>Results:</b> The inhibitory activity (IC₅₀) of ethanol extract and ethyl acetate fraction of <i>A. conyzoides</i> against iNOS was 92.05 and 4.78 µg mL¹, respectively. Pearson correlation analysis resulted in 0.548 (ethanol extract) and 0.696 (ethyl acetate fraction). The total flavonoids (calculated as quercetin) contained in the ethanol extract and ethyl acetate fraction of <i>A. conyzoides</i> were 0.71 and 7.65%, respectively. The FLS in <i>A. conyzoides</i> leaves was identified at 31 kDa. <b>Conclusion:</b> <i>A. </i>c<i>onyzoides</i> L. is potential in inhibiting iNOS due to quercetin contained in the leaves. This report will add a scientific insight of <i>A. conyzoides</i> for biological sciences.

Ageratum conyzoides L. and Its Secondary Metabolites in the Management of Different Fungal Pathogens.

Ageratum conyzoides L. (Family-Asteraceae) is an annual aromatic invasive herb, mainly distributed over the tropical and subtropical regions of the world. It owns a reputed history of indigenous remedial uses, including as a wound dressing, an antimicrobial, and mouthwash as well as in treatment of dysentery, diarrhea, skin diseases, etc. In this review, the core idea is to present the antifungal potential of the selected medicinal plant and its secondary metabolites against different fungal pathogens. Additionally, toxicological studies (safety profile) conducted on the amazing plant A. conyzoides L. are discussed for the possible clinical development of this medicinal herb. Articles available from 2000 to 2020 were reviewed in detail to exhibit recent appraisals of the antifungal properties of A. conyzoides. Efforts were aimed at delivering evidences for the medicinal application of A. conyzoides by using globally recognized scientific search engines and databases so that an efficient approach for filling the lacunae in the research and development of antifungal drugs can be adopted. After analyzing the literature, it can be reported that the selected medicinal plant effectively suppressed the growth of numerous fungal species, such as Aspergillus, Alternaria, Candida, Fusarium, Phytophthora, and Pythium, owing to the presence of various secondary metabolites, particularly chromenes, terpenoids, flavonoids and coumarins. The possible mechanism of action of different secondary metabolites of the plant against fungal pathogens is also discussed briefly. However, it was found that only a few studies have been performed to demonstrate the plant's dosage and safety profile in humans. Considered all together, A. conyzoides extract and its constituents may act as a promising biosource for the development of effective antifungal formulations for clinical use. However, in order to establish safety and efficacy, additional scientific research is required to explore chronic toxicological effects of ageratum, to determine the probability of interactions when used with different herbs, and to identify safe dosage. The particulars presented here not only bridge this gap but also furnish future research strategies for the investigators in microbiology, ethno-pharmacology, and drug discovery.

Fractions of Ageratum conyzoides L. (Compositae) induce mitochondrial-mediated apoptosis in rats: Possible option in monosodium glutamate-induced hepatic and uterine pathological disorder.

ETHNOPHARMACOLOGICAL RELEVANCE: Several pathological disorders have been attributed to either oxidative stress or defect in apoptotic signaling pathway. Some bioactive compounds elicit their antiproliferative properties by induction of apoptosis via mitochondrial permeability transition (mPT) pore opening. AIM OF STUDY: The present study therefore investigated the effects of various fractions of methanol extract of Ageratum conyzoides L. (MEAC) on mitochondrial-mediated apoptosis and the possible protective potential of the most potent against monosodium glutamate (MSG)-induced hepatic damage and uterine pathological disorder. The plant is folklorically used in the treatment of cancer and gynecological disorder. MATERIALS AND METHODS: The MEAC was partitioned in succession and concentrated at 40 °C to obtain chloroform(CFAC), ethylacetate(EFAC) and methanol(MFAC) fractions. Mitochondria were isolated by differential centrifugation. The opening of mPT pore, mATPase activity and hepatic DNA fragmentation were assessed spectrophotometrically. Caspases 9 and 3, SOD and GSH-Px activities and MDA level were determined using ELISA technique. Histological assessment of the liver and uterine sections and GC-MS analysis of the most potent fraction were carried out. RESULTS: The investigation showed that oral administration of the fractions caused induction of mPT pore opening, enhanced mATPase activity, upregulated the activities of caspases 9 and 3 and also, caused hepatic DNA fragmentation with CFAC being the most potent. The CFAC reversed severe MSG-induced hepatic damage and uterine hyperplasia. The MSG-induced oxidative stress was normalized by CFAC. The GC-MS analysis of CFAC revealed the presence of some pharmacologically relevant phytochemicals. CONCLUSION: These findings therefore suggest that fractions of Ageratum conyzoides induce mitochondrial-mediated apoptosis. Moreover, CFAC, which is the most potent has a promising antioxidant and antiproliferative potential against MSG-induced hepatic and uterine pathological disorder.

Effectiveness of different methods for the extraction of principle actives and phytochemicals content in medicinal herbals / Efectividad de diferentes métodos para la extracción de principios activos y contenido de fitoquímicos en hierbas medicinales

In this present study, we investigated the influence of various extraction methods including maceration, sonication, infusion, decoction, and microwave extraction, on the chemical and biological potential of phytochemicals extracted from three medicinal plants (Ageratum conyzoides, Plantago majorand Arctium lappa L). The results were subsequently analyzed by variance analysis. Our results suggested that sonication is the most effective extraction method among the five methods tested herein, for the extraction of phytochemicals that have a high antioxidant potential and high phenolic content. The three plants employed for this study had a high concentration of flavonoids and phenolics which was compatible with the chemosystematics of the species. All the samples possessed a Sun Protection Factor (SPF) of less than 6. Interestingly, a maximum reaction time of approximately 20 min was noted for the complexation of AlCl3 with the flavonoids present in the phytochemical extract during analyses of the kinetic parameters. We finally identified that the Ageratum conyzoides extract, prepared by sonication, possessed a significant pharmacological potential against hepatocarcinoma tumour cells, whose result can guide further studies for its therapeutic efficacy.

En el presente estudio, investigamos la influencia de varios métodos de extracción, incluyendo maceración, sonicación, infusión, decocción y extracción por microondas, sobre el potencial químico y biológico de los fitoquímicos extraídos de tres plantas medicinales (Ageratum conyzoides, Plantago majory Arctium lappa L). Los resultados se analizaron posteriormente mediante análisis de varianza. Nuestros resultados sugieren que la sonicación es el método de extracción más eficaz entre los cinco métodos aquí probados, para la extracción de fitoquímicos que tienen un alto potencial antioxidante y un alto contenido fenólico. Las tres plantas empleadas para este estudio tenían una alta concentración de flavonoides y fenólicos que era compatible con la quimiosistemática de las especies. Todas las muestras poseían un factor de protección solar (SPF) menor a 6. Curiosamente, se observó un tiempo máximo de reacción de aproximadamente 20 min para la complejación de AlCl3con los flavonoides presentes en el extracto fitoquímico durante los análisis de los parámetros cinéticos. Finalmente, identificamos que el extracto de Ageratum conyzoides, elaborado por sonicación, posee un importante potencial farmacológico frente a las células tumorales del hepatocarcinoma, cuyo resultado puede orientar nuevos estudios sobre su eficacia terapéutica.

Development of an efficient antitick natural formulation for the control of acaricide-resistant ticks on livestock.

Animal production has a key role in global economic development and food security. Ticks, specifically Rhipicephalus microplus cause substantial economic and health impacts on more than eighty percent of the world cattle population. Though synthetic acaricides play a major role in tick management, their injudicious usage has caused environmental pollution and also promote the establishment of multi-acaricide resistant tick populations which is a matter of great concern. To provide an effective tool for controlling these resistant ticks, the present work was aimed to develop safe and inexpensive antitick natural formulations. Our bioprospection studies of Ageratum conyzoides plant established it as a species potentially having strong acaricidal activity due to the presence of potent acaricidal phyto-chemicals. To develop a suitable antitick natural formulation, 41 samples/fractions/formulations were prepared from the dry powder of the whole aerial part of the A. conyzoides plant using different techniques and delivery matrices. The strongest antitick effect was recorded for formulation ACF6, which demonstrated 87 ± 6% mean mortality with 57 % inhibition of oviposition in treated female ticks. Ticks treated with the ACF6 formulation showed a significant (p < 0.001) reduction in cuticular protein (1.238 ± 0.01 mg/mL) as compared to control ticks (2.928 ± 0.01 mg/mL) but no significant difference in chitin content of treated ticks and control ticks was observed. The formulation was found safe in a rat model as no significant differences in biochemical and haematological parameters among treated and control rats were noted. Histopathological studies indicated no sign of hepatocellular necrosis and no significant changes in the weights of liver and spleen was recorded. The overall in vivo efficacy of the formulation was 85 % for experimentally infested cattle with direct mortality of more than 80 % within 96 h post-application. The lethal effect of the formulation was in the form of drying and dead ticks 1-2 d after application. The developed formulation has the potential to be adopted as an alternative tick control measure in an ecofriendly manner.

Anti-Neuropathic Pain Activity of Ageratum conyzoides L due to the Essential Oil Components.

BACKGROUND: Neuropathic pain is one of the contributors to the global burdens of illness. At present many patients do not achieve satisfactory pain relief even with synthetic painkillers. Taking this into consideration, it is necessary to search for natural product-derived alternative treatment with confirmed safety and efficacy. Ageratum conyzoides L is a plant often used as an analgesic in Indonesia, however, anti-neuropathic pain activity of this plant is still unknown. OBJECTIVE: To determine the anti-neuropathic pain activity of the essential oil and non-essential oil component (distillation residue) of A. conyzoides L. METHODS: We conducted the separation of the essential oil component from other secondary metabolites through steam distillation. Both components were tested for anti-neuropathic pain activity using chronic constriction injury animal models with thermal hyperalgesia and allodynia tests. The animals were divided into 7 test groups, namely normal, sham, negative, positive (pregabalin at 0.195 mg/20 g BW of mice), essential oil component (100 mg/kg BW), and non-essential oil component (100 mg/kg BW). Naloxone was tested against the most potent anti-neuropathic pain component (essential oil or non-essential oil) to investigate the involvement of opioid receptors. RESULTS: The GC-MS of the essential oil component indicated the presence of 60 compounds. Meanwhile, non-essential oil components include alkaloid, flavonoid, polyphenol, quinone, steroid, and triterpenoid. This non-essential oil component contained a total flavonoid equivalent to 248.89 ppm quercetin. The anti-neuropathic pain activity test showed significantly higher activity of the essential oil component compared to the non-essential oil component and negative groups (p<0.05). Furthermore, the essential oil component showed equal activity to pregabalin (p>0.05). However, this activity was abolished by naloxone, indicating the involvement of the opioid receptor in the action of the essential oil component. CONCLUSION: The essential oil component of A. conyzoides L is a potential novel substance for use as anti-neuropathic pain.