Chromatographic Method for Monitoring of Pesticide Residues and Risk Assessment for Herbal Decoctions Used in Traditional Korean Medicine Clinics.

The presence of pesticide residues in herbs and the herbal products derived from them raises serious health concerns. This study was conducted to investigate the residual pesticide concentrations and assess potential human health risks from herbal medicines used in traditional Korean medicine clinics. A total of 40 samples of herbal decoctions were collected from 10 external herbal dispensaries. The pesticide residues were analyzed by the multiresidue method for 320 different pesticides using liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS). As a result of the monitoring, carbendazim was detected at 0.01 and 0.03 µg/g in eight samples and no pesticide was detected in the other herbal decoctions. Carbendazim was set for each individual item as less than 0.05 µg/g in Paeoniae radix, less than 0.05 µg/g in Cassiae semen, less than 2.0 µg/g in Lycii fructus, and less than 10 µg/g in Schisandrae fructus (dried). Therefore, the results of this study suggested that the detected pesticide residues in herbal decoctions could not be considered as posing a serious health risk.

[Study on Ranunculaceae herbal decoction pieces using X-ray diffraction].

The powder X-ray diffraction(PXRD) technique was used to investigate fourteen kinds of Ranunculaceae herbal decoction pieces(RHDP) recorded in Chinese Pharmacopoeia and to explore a novel PXRD quality control method for RHDP. The results indicated that only three RHDP-Paeoniae Radix Alba, Paeoniae Radix Rubra, and Moutan Cortex, contained calcium oxalate monodydrate(COM), whereas no COM existed in other eleven kinds of RHDP. The difference in PXRD for Paeoniae Radix Alba and Paeoniae Radix Rubra from different growing areas were investigated. The quantitative analysis method for COM was discussed by considering the water-boiling manufacturing process of herbal decoction pieces. The water-boiling experiments revealed that the PXRD peaks from COM crystals in RHDP were enhanced significantly after boiling. Paeoniae Radix Alba, Paeoniae Radix Rubra, Moutan Cortex, Aconiti Lateralis Radix Praeparata, Aconiti Radix, Aconiti Kusnezoffii Radix, and Anemone Raddeanae Rhizoma exhibited a similar series of broader peaks in the 2θ region of 15° to 35°, whose origins were discussed on the basis of chemical constituents RHDP reported by other researchers. These diffraction broader peaks most likely originated from periodic orientation of benzene ring in organic molecular crystals of aconitine-and paeonolum-based alkaloids and glycosides chemical constituents, subsequently, possibly from some other organic constituents. The PXRD technique can be used to rapidly identify Cimicifuga heracleifolia with an amorphous dispersion peak and C. dahurica with a sharp-peak feature. Climatidis Radix et Rhizoma exhibited a series of sharp PXRD peaks. The PXRD method can provide a valuable quality control method for RHDP.

Aeginetia indica Decoction Inhibits Hepatitis C Virus Life Cycle.

Chronic hepatitis C virus (HCV) infection is still a global epidemic despite the introduction of several highly effective direct-acting antivirals that are tagged with sky-high prices. The present study aimed to identify an herbal decoction that ameliorates HCV infection. Among six herbal decoctions tested, the Aeginetia indica decoction had the most profound effect on the HCV reporter activity in infected Huh7.5.1 liver cells in a dose- and time-dependent manner. The Aeginetia indica decoction exerted multiple inhibitory effects on the HCV life cycle. Pretreatment of the cells with the Aeginetia indica decoction prior to HCV infection reduced the HCV RNA and non-structural protein 3 (NS3) protein levels in the infected cells. The Aeginetia indica decoction reduced HCV internal ribosome entry site-mediated protein translation activity. It also reduced the HCV RNA level in the infected cells in association with reduced NS5A phosphorylation at serine 235, a predominant phosphorylation event indispensable to HCV replication. Thus, the Aeginetia indica decoction inhibits HCV infection, translation, and replication. Mechanistically, the Aeginetia indica decoction probably reduced HCV replication via reducing NS5A phosphorylation at serine 235.

Monitoring heavy metals, residual agricultural chemicals and sulfites in traditional herbal decoctions.

BACKGROUND: Asian traditional herbal preparations are frequently considered for the contamination with undeclared toxic or hazardous substances. The aim of this study was to determine the toxic heavy metals, pesticides and sulfur dioxide in decoctions that is a common form of final utilization in Korea. METHODS: A total of 155 decoctions composed of multi-ingredient traditional herbs were randomly sampled from Seoul in Korea between 2013 and 2014. For each decoction, the concentrations of four heavy metals (arsenic, cadmium, lead and mercury), 33 pesticides and sulfur dioxide were analyzed using inductively coupled plasma mass spectrometry (ICP-MS), mercury analyzer, gas chromatography/nitrogen phosphorous detector (GC/NPD), gas chromatography/micro electron capture detector (GC/µECD), and Monier-Williams method respectively. RESULTS: One hundred fifty-two of One hundred fifty-five decoctions (98.1%) contained one of three heavy metals (96.1% for As, 97.4% for Cd, and 90.3% for Pb, 0.0% for Hg). Their average concentrations (77.0 ± 79.7 ug/kg for As, 20.4 ± 23.7 ug/kg for Cd, and 68.8 ± 76.5 ug/kg for Pb) were approximately 20% of the maximum allowable limits of vegetable or ginseng beverage described in the Korean Food Standard Codex while their 95th percentile concentrations were below than the guideline for them. None of 33 pesticides was detected in 155 decoction samples, and only one sample showed over limit of detection for residual sulfites. CONCLUSIONS: This study support that the contained status of toxic heavy metals, pesticides and sulfur dioxide in herbal decoctions are currently within safe level in Korea, and provide a reference data for the further studies focused on the safety herbal preparations.

[Thermodynamic analysis of water adsorption and desorption process of Chinese herbal decoction pieces].

Based on the basic theory of thermodynamics, the thermodynamic parameters and related equations in the process of water adsorption and desorption of Chinese herbal decoction pieces were established, and their water absorption and desorption characteristics were analyzed. The physical significance of the thermodynamic parameters, such as differential adsorption enthalpy, differential adsorption entropy, integral adsorption enthalpy, integral adsorption entropy and the free energy of adsorption, were discussed in this paper to provide theoretical basis for the research on the water adsorption and desorption mechanism, optimum drying process parameters, storage conditions and packaging methods of Chinese herbal decoction pieces.

Chinese herbal medicine for irinotecan-induced diarrhea: A systematic review and meta-analysis.

INTRODUCTION: Irinotecan is a novel first-line therapy for colorectal cancer, but the toxicity and side effects include diarrhea without satisfactory treatments. Chinese herbal decoction (CHD) is an effective complementary and alternative prevention and therapy for irinotecan induced diarrhea (IID). This systematic review and meta-analysis of randomized controlled trials (RCTs) aims to assess the preventive effect of CHD in the treatment of IID. METHODS: Seven databases (PubMed, COCHRANE, EMBASE, CNKI, VIP, Wanfang, and CBM) were screened for random controlled trials on the prevention and treatment of IID by CHD from January 1980 to May 2022. The Cochrane Collaboration Risk of Bias (ROB 2.0) was applied for bias risk assessment, and the Grading Recommendation Assessment, Development, and Evaluation (GRADE) for quality of evidence. Meta-analysis was conducted with RevMan 5.3 software. In addition, a subgroup analysis was conducted on different grades of diarrhea, the incidence and duration of diarrhea, the selection of specific Chinese herbal medicine decoction, and the incidence of adverse reactions. Risk ratios (RR) and 95% confidence intervals (CIs) were calculated for all data by combining the meta-analysis with fixed or random-effects models based on outcome heterogeneity. RESULTS: Fourteen RCTs involving 1056 participants were included. The study results displayed that the incidence of IID was lower with the use of CHD than the no-treatment group (RR = 0.55, 95% CI = 0.40-0.75, P = 0.0002). CHD in combination with western medicine (WM) was more effective than WM alone for IID (RR = 0.44, 95% CI 0.23-0.84, P = 0.01). This protective effect was more pronounced for severe grade III-V diarrhea (RR = 0.41, 95% CI = 0.26-0.64, P < 0.0001). In the specific Chinese herbal medicine decoction, the Banxia Xie Xin decoction presented better effectiveness (RR = 0.18, 95% CI: 0.05-0.63, P = 0.007) than WM alone. The Huangqin decoction was the most widely studied interventional scheme (n = 5). The relative risk (RR) of the Huangqin decoction was 0.56. No obvious adverse reactions were observed. CONCLUSION: This study demonstrated that CHD has a preventive effect on IID and could be used as a complementary therapy with few side effects. However, additional large-sample, high-quality, randomized, double-blind trials are needed to guide the clinical practice scientifically. SYSTEMATIC REVIEW REGISTRATION: www.crd.york.ac.uk/prospero (NO: CRD42020189506).

Adverse events of herbal decoction: A systematic review and meta-analysis over past 10 years.

BACKGROUND: Herbal decoctions (HDs) are the oldest and most common herbal medicine formulations. Different HDs exist, and some consumers are concerned that they may become contaminated during manufacturing. Therefore, the need for a safety assessment of HDs has been raised. This study aimed to investigate the adverse events (AEs) associated with HDs by comprehensively analyzing randomized controlled trials (RCTs) using systematic reviews and meta-analyses. METHODS: A systematic search was conducted on PubMed, Embase, and the Cochrane Library for articles published up to November 2022. The included RCTs compared HDs with other treatments published between 2013 and 2022, and the risk of bias was assessed using RevMan 5.4. Meta-analyses of the number of AEs associated with HDs reported in the included RCTs were also performed. RESULTS: The systematic review included 26 RCTs, and the meta-analysis included 17 RCTs that reported AEs. The meta-analysis comparing HDs with active controls showed that both the number of AEs (14 studies; risk ratio (RR)= 0.50 cases, 95 % confidence interval (CI) [0.29, 0.88]; I2 = 42 %) and the number of patients who complained of AEs (seven studies; RR=0.51 patients, 95 % CI [0.28, 0.94]; I2 =9 %) were fewer in the HDs group than in the active control groups. CONCLUSION: This study showed that HDs are safer than other conventional medications based on the results of qualitative and quantitative syntheses of RCTs.

Use of Herbal Decoction and Pharmacopuncture in Individuals with Chronic Disease: findings from a nationally representative panel.

Objectives: This study analyzed the Korea Health Panel Annual Data 2019 to investigate factors related to the use of non-insured Korean medicine (KM) treatment in individuals with chronic diseases. The non-insured KM treatments of interest were herbal decoction (HD) and pharmacopuncture (PA). Methods: Among adults aged 19 or older, 6,159 individuals with chronic diseases who received outpatient KM treatment at least once in 2019 were included. They were divided into three groups according to the KM treatment used (1) basic insured KM non-pharmacological treatment (BT) group (n = 629); (2) HD group (n = 256); (3) PA group (n = 184). Logistic regression analysis was used to explore factors associated with favoring HD or PA use over BT. Potentially relevant candidate factors were classified using the Andersen Behavior Model. Results: Compared to BT, the 1st to 3rd quartiles of income compared to the 4th quartile (odds ratio 1.50 to 2.06 for HD; 2.03 to 2.83 for PA), health insurance subscribers compared to medical aid (odds ratio 2.51; 13.43), and presence of musculoskeletal diseases (odds ratio 1.66; 1.91) were significantly positively associated with HD and PA use. Moreover, the presence of cardiovascular disease (odds ratio 1.46) and neuropsychiatric disease (odds ratio 1.97) were also significantly positively associated with HD use. Conclusion: The presence of some chronic diseases, especially musculoskeletal diseases, was significantly positively associated with HD and PA use, while low economic status was significantly negatively associated with HD and PA use, indicating the potential existence of unmet medical needs in this population. Since chronic diseases impose a considerable health burden, the results of this study can be used for reference for future health insurance coverage policies in South Korea.

Satisfaction and Perceived Effectiveness on Herbal Decoctions for Postpartum Care: a cross-sectional survey of mother's experience.

Objectives: In East Asia, postpartum care has traditionally been considered important for maternal health; however, studies on this are still insufficient. Therefore, we examined the satisfaction and perceived effectiveness of herbal decoctions used in postpartum care in a city in the Republic of Korea (ROK). Methods: We analyzed anonymized secondary data obtained from a retrospective cross-sectional survey of women who had taken herbal decoctions provided by the support service for women giving birth in a local city in ROK. The questionnaire items consisted of basic information regarding childbirth, the need for the herbal decoction support service, satisfaction, and the effectiveness of the service received. Results: A total of 68 women were included in the study, and those aged 30-39 accounted for 73.13%. Of the 68 women, 79.37% visited within 3 weeks of childbirth. Women's satisfaction regarding herbal decoction support for postpartum care was 76.47%, and most women (98.53%) responded that they needed it more than twice. More than 50% of women showed improvement in puerperal wind disorders, weight gain, and delayed eliminated lochia. Conclusion: A large proportion of women who took herbal decoctions reported satisfaction and perceived effectiveness when used to treat puerperal wind disorders. Nevertheless, future well-designed clinical studies are needed to provide information on whether herbal decoctions effectively prevent and treat puerperal wind disorders.

A comprehensive analysis of the Bencao (herbal) small RNA Atlas reveals novel RNA therapeutics for treating human diseases.

Cross-kingdom herbal miRNA was first reported in 2012. Using a modified herbal extraction protocol, we obtained 73,677,287 sequences by RNA-seq from 245 traditional Chinese Medicine (TCM), of which 20,758,257 were unique sequences. We constructed a Bencao (herbal) small RNA (sRNA) Atlas ( http://bencao.bmicc.cn ), annotated the sequences by sequence-based clustering, and created a nomenclature system for Bencao sRNAs. The profiles of 21,757 miRNAs in the Atlas were highly consistent with those of plant miRNAs in miRBase. Using software tools, our results demonstrated that all human genes might be regulated by sRNAs from the Bencao sRNA Atlas, part of the predicted human target genes were experimentally validated, suggesting that Bencao sRNAs might be one of the main bioactive components of herbal medicines. We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions. Moreover, the decoctosome, a lipo-nano particle consisting of 0.5%-2.5% of the decoction, demonstrated potent medical effects. We propose a Bencao (herbal) Index, including small-molecule compounds (SM), protein peptides (P), nucleic acid (N), non-nucleic and non-proteinogenic large-molecule compounds (LM) and elements from Mendeleev's periodic table (E), to quantitatively measure the medical effects of botanic medicine. The Bencao sRNA Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine, and may provide potential remedies for the theory and practice of one medicine.

Monitoring of Heavy Metals and Pesticide Residues of Herbal Decoctions in Traditional Korean Medicine Clinics in Korea.

In this study, we investigated whether the levels of heavy metal and pesticide residues in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for heavy metal content such as lead, arsenic, and cadmium using inductively coupled plasma optical emission spectrometry. For mercury, an automatic mercury analyzer based on the gold amalgamation process was used. For pesticide residues, gas chromatography with electron capture detection and gas chromatography with mass selective detection were used for the analyses. Based on the testing, heavy metals were identified in most of the decoctions (Cd: 0.000-0.003 ppm, Pb: 0.003-0.023 ppm, As: 0.000-0.016 ppm, Hg: 0.000-0.002 ppm). Pesticide residues (e.g., total DDT, total BHC, aldrin, endrin, dieldrin) were not detected at all. All of these were no more than the limit values in preceding studies. Therefore, this study confirms that the contents of heavy metals and pesticides in herbal decoctions are within safe levels based on a previous study and provides evidence for establishing safety management standards for herbal decoctions in Korea.

Herbal Decoctions for the Levels of Sulfur Dioxide, Benzopyrene, and Mycotoxin from Traditional Korean Medicine Clinics: A Preliminary Study.

In this study, we investigated whether the levels of sulfur dioxide (SO2), benzopyrene, and mycotoxins in herbal decoctions in Korea in 2019 were within normal limits. In total, 30 decoctions composed of multi-ingredient traditional herbs were sampled from traditional Korean medicine (TKM) clinics, TKM hospitals, and external herbal dispensaries in 2019. The decoctions were analyzed for SO2, benzopyrene, and mycotoxins using 10 samples. SO2 and benzopyrene were not detected in any of the herbal decoctions. With regard to mycotoxins, aflatoxin B1 was not detected, but B2 was detected in 7 cases (0.00~0.04 ppb), G1 in 13 cases (0.03~0.29 ppb), and G2 in 9 cases (0.02~0.93 ppb). None of these values exceeded the restrictions in prior studies. Thus, we confirm that the amounts of SO2, benzopyrene, and mycotoxins in herbal decoctions are at safe levels and provides the basis of establishing safety management criteria for herbal decoctions.

Synergistic effects of novel herbal decoctions from Panax ginseng and Morus alba on tyrosinase activity and melanogenesis in vitro.

Many medicinal plants such as a Panax ginseng and Morus alba (mulberry tree) have been widely used as depigmenting agents in Asia. To maximize their synergistic effects on melanogenesis, new herbal decoctions were created by mixing Ginseng Radix Alba (GR) and Mori Radicis Cortex (MC) at a ratio of 3:2 which called GMC decoction. A decoction of GR and Mori Ramulus (MR), which called GMR, was also formulated in order to compare the anti-melanogenic capacity. Combined decoctions, GMC and GMR, significantly decreased mushroom tyrosinase activity in vitro; however, single extracts, including MC and MR, showed weaker inhibitory activity. Melanin content assay and Fontana-Masson staining confirmed that two decoctions showed stronger inhibitory effects on the forskolin-induced melanin level in B16 cells, without cytotoxicity. Our findings suggest that ginseng in combination with mulberry tree enhances the anti-melanogenic effect in vitro.

Possible role of Unani Pharmacology in COVID-19 - a narrative review.

According to the World Health Organization (WHO), viral diseases continue to rise, and pose a significant public health problem. Novel coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2. The pathogenesis and clinical manifestations of COVID-19 is close to Amraz-e-Wabai (epidemic diseases) which was described by Hippocrates, Galen, Aristotle, Razes, Haly Abbas, Avicenna, Jurjani etc. Presently, there is no specific or challenging treatment available for COVID-19. Renowned Unani Scholars recommended during epidemic situation to stay at home, and fumigate the shelters with aromatics herbs like Ood kham (Aquilaria agallocha Roxb.), Kundur (Boswellia serrata Roxb), Kafoor (Cinnamomum camphora L.), Sandal (Santalum album L), Hing (Ferula foetida L.) etc. Use of specific Unani formulations are claimed effective for the management of such epidemic or pandemic situation like antidotes (Tiryaqe Wabai, Tiryaqe Arba, Tiryaqe Azam, Gile Armani), Herbal Decoction (Joshandah), along with Sharbate Khaksi, Habbe Bukhar, Sharbate Zanjabeel, Khamira Marwareed, Jawarish Jalinus, and Sirka (vinegar). Such drugs are claimed for use as antioxidant, immunomodulatory, cardiotonic, and general tonic actions. The study enumerates the literature regarding management of epidemics in Unani medicine and attempts to look the same in the perspective of COVID-19 prevention and management.

Divya-Herbal-Peya Decoction Harmonizes the Inflammatory Response in Lipopolysaccharide-Induced Zebrafish Model.

BACKGROUND: Divya-Herbal-Peya (DHP) is a plant-based decoction containing fourteen herbs in precise quantities; usually prescribed by the practitioners in Ayurveda to alleviate stress and minimize the exasperating symptoms of recurring infections. Our study aims to provide an experimental validation to the immunomodulatory properties of DHP. METHODS: Physico-chemical analysis of DHP was performed to evaluate the presence of secondary metabolites. The phytochemicals were then identified and quantitated through HPTLC, UHPLC, and GC-MS techniques. To address the scientific rationale behind DHP, lipopolysaccharide (LPS) was intraperitoneally injected in adult zebrafish to develop inflammatory response. Following LPS-induction, abnormality in locomotory behaviour was determined by evaluating the relative swim velocity and the rate of turning in experimental zebrafish. Pathophysiological effects were determined through opercular frequency, behavioural fever, and caudal fin damage. LPS-mediated inflammation was measured of pro-inflammatory cytokines, TNFα, IL-6, and IL-1ß expression in the serum of study animals, by RT-PCR. RESULTS: Our study phytochemically characterized and ascertained the presence of glycyrrhizin, rosmarinic acid, gingerol, cinnamic acid, protocatechuic acid, gallic acid, ellagic acid, piperine and cinnamaldehyde in DHP decoction. LPS induced aberrant locomotory patterns, behavioural fever and caudal fin damage in zebrafish. A significant increase in gene expression levels of pro-inflammatory cytokines, TNFα, IL-6, and IL-1ß was also determined. However, these locomotory deviations and behavioural fever were negligible in zebrafish groups pre-administered either with DHP in a dose dependent manner or dexamethasone (DEX). The altered opercular rate, caudal fin damage and elevated transcription levels of pro-inflammatory genes upon LPS-induction were averted in groups pre-treated with DHP and DEX. CONCLUSION: DHP prophylactically prevented the LPS-induced abnormal behaviour and inflammation-related pathophysiology in zebrafish. Immunomodulatory properties of DHP may not have therapeutic intervention, but do confer nutraceutical health benefits against mild infections.

The effect of Salaciareticulata, Syzygiumcumini, Artocarpusheterophyllus, and Cassiaauriculata on controlling the rapid formation of advanced glycation end-products.

BACKGROUND: The excessive formation of Advanced Glycation End-products (AGEs) by non-enzymatic glycation mediates many health complications in the human body and the formation of AGEs largely accelerated under the hyperglycaemic condition. OBJECTIVE: The prospect of the study to assess the strength of inhibiting the rapid AGE formations in four Ayurvedic medicinal plants, namely; Salacia reticulata (stems), Syzygium cumini (barks), Artocarpus heterophyllus (mature leaves) and, Cassia auriculata (flowers). MATERIALS AND METHODS: Herbal decoctions of four medicinal plant materials were prepared by simmering with hot water as prescribed by the Ayurvedic medicine. The effectiveness of the decoctions was analyzed in vitro based on their Anti-AGE formation activity, glycation reversing, and anti-oxidant potentials. RESULTS: According to the results, the decoctions of S. reticulata, A. heterophyllus and C. auriculata indicated the strong Anti-AGE forming (IC50: 23.01 ± 2.70, 32.01 ± 2.09, 43.66 ± 2.11 mg/mL, respectively), glycation reversing (EC50: 183.15 ± 7.67, 91.85 ± 1.93, 252.35 ± 4.03 mg/mL, respectively) and antioxidant potentials in terms of total polyphenol content (TPC), total flavonoid content (TFC), ferric ion reducing power (FRAP), ABTS and DPPH radical scavenging activities. However, the decoction of S. cumini reported the significantly high (p < 0.05) Anti-AGE forming, (IC50: 9.75 ± 0.32 mg/mL), glycation reversing (EC50: 66.45 ± 4.51 mg/mL), and antioxidant potentials against the decoctions of the other three plant materials. CONCLUSION: S. cumini bark extract was identified as the best source in controlling the formation of AGEs excessively. Further, the other three plant extracts can also be effectively used as potential therapeutic agents to control the pathological conditions associated with AGEs-mediated health complications.

The efficacy of Siddha Medicine, Kabasura Kudineer (KSK) compared to Vitamin C & Zinc (CZ) supplementation in the management of asymptomatic COVID-19 cases: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine. TRIAL DESIGN: A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial. PARTICIPANTS: Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded. INTERVENTION AND COMPARATOR: Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days. MAIN OUTCOMES: The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes. RANDOMISATION: The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures. BLINDING (MASKING): This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm. TRIAL STATUS: Protocol version 2.0 dated 16th May 2020. Recruitment is completed. The trial started recruitment on the 25th May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection TRIAL REGISTRATION: The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Herbal Decoction Divya-Peedantak-Kwath Alleviates Allodynia and Hyperalgesia in Mice Model of Chemotherapy-Induced Peripheral Neuropathy via Modulation in Cytokine Response.

The widely used cancer treatment, chemotherapy, causes severe long-term neuropathic pain in 30-40% cases, the condition clinically known as chemotherapy-induced peripheral neuropathy (CIPN). Approved conventional analgesics are sometimes ineffective, while others like opioids have undesirable side effects like addiction, seizures, and respiratory malfunctioning. Tricyclic antidepressants and anticonvulsants, although exhibit anti-allodynic effects in neuropathy, also have unpleasant side effects. Thus, alternative medicines are being explored for CIPN treatment. Despite scattered reports on different extracts from different plants having potential anti-allodynic effects against CIPN, no established medicine or formulation of herbal origin exists. In this study, efficacy of an herbal decoction, formulated based on ancient medicinal principles and protocols for treating neuropathic pain, Divya-Peedantak-Kwath (DPK), has been evaluated in a paclitaxel (PTX)-induced peripheral neuropathic mouse model. We observed that DPK has prominent anti-allodynic and anti-hyperalgesic effects and acts as a nociceptive modulator for CIPN. With exhibited antioxidative effects, DPK restored the redox potential of the sciatic nerves to the normal. On histopathological evaluation, DPK prevented the PTX-induced lesions in the sciatic nerve, in a dose-dependent manner. It also prevented inflammation by modulating the levels of pro-inflammatory cytokines involved in CIPN pathogenesis. Our observations evinced that DPK can alleviate CIPN by attenuating oxidative stress and concomitant neuroinflammation through immune modulation.

Pro-angiogenic activity of Tongnao decoction on HUVECs in vitro and zebrafish in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongnao Decoction (TND) is a Chinese decoction approved and used in Jiangsu Province Hospital for the treatment of ischemic stroke. It shows conclusive efficiency in the improvement of neurologic impairment and activities of daily living of the patients. AIM OF THE STUDY: Recently, angiogenesis has been recognized as a potential therapeutic strategy for treating cerebral ischemia. This study was aimed to provide comprehensive evidence for the pro-angiogenic effect of TND and characterize the underlying mechanism. MATERIALS AND METHODS: We firstly established the chemical fingerprinting of TND. Then, the in vitro pro-angiogenic activities of TND were tested on human umbilical vein endothelial cells (HUVECs) through cell viability, wound healing and tube formation assays. The in vivo pro-angiogenic effects were evaluated on transgenic zebrafish embryos [Tg (fli-1: EGFP)] through the formation of intersegmental vessels (ISVs), subintestinal vessels (SIVs) and central arteries (CtAs). Lastly, the potential mechanisms of TND were analyzed by a blocking assay with eight pathways-specific kinase inhibitors. RESULTS: TND promoted the proliferation, migration and tube formation of HUVECs. TND also rescued the impairment of ISVs, SIVs and CtAs caused by VRI in a dose-dependent manner in zebrafish embryos. TND could activate vascular endothelial growth factor receptor-2 (VEGFR-2), phosphoinositide 3-kinase (PI3K) - protein kinase B (Akt) and Raf - mitogen-activated protein kinase1/2 (MEK1/2) - extracellular regulated kinase 1/2 (ERK1/2) signaling pathways. CONCLUSION: Our study firstly demonstrated the pro-angiogenic activities of TND. Our work provided evidences for the clinical usage of TND in restoring neurovascular function through promoting angiogenesis in the ischemic cerebral microvascular.

Herbal decoction Divya-Swasari-Kwath attenuates airway inflammation and remodeling through Nrf-2 mediated antioxidant lung defence in mouse model of allergic asthma.

BACKGROUND AND PURPOSE: Asthma is a chronic respiratory disease orchestrated by immune and structural cells. Identification of novel therapeutic strategies are needed for asthma due to the limitations of existing therapies. We have validated the anti-inflammatory, anti-asthmatic and immunomodulatory therapeutic properties of herbal decoction, Divya-Swasari-Kwath (DSK) using mouse model of ovalbumin (OVA) induced allergic asthma. METHODS AND RESULTS: HPLC analysis identified the presence of Rutin, Glycyrrchzin, Gallic acid, Cinnamic acid, Chlorogenic acid, Caffeic acid and Piperine as bioactive herbal metabolites in DSK. Therapeutic treatment with herbal decoction DSK significantly alleviated the pathological features of allergic asthma including inflammatory cell accumulation in Broncho-Alveolar Lavage (BAL) fluids, specifically lymphocytes and eosinophils, lung inflammation, oxidative stress, airway remodelling, and pro-inflammatory cytokine levels. H&E analysis of lung tissue sections identified attenuated inflammatory cell infiltration and thickening of bronchial epithelium by DSK. PAS staining and MT staining identified decrease in OVA-induced mucus hyper secretion and peri-bronchial collagen deposition respectively, upon DSK treatment. Treatment with DSK increased the mRNA expression of antioxidative defence gene Nrf-2 and its downstream target genes HO-1 and NQO-1. In the same line, biochemical analysis for the markers of oxidative/antioxidant system confirmed the restoration of activity of Catalase, GPx, SOD and EPO and the levels of GSH, GSSG, MDA and Nitrite in whole lungs. In line with PAS staining, DSK treatment decreased the OVA-induced expression of Muc5AC and Muc5B genes. DSK treatment reduced the steady state mRNA expression levels of IL-6, IL-1ß, TNF-α, IL-4, -5, -33, IFN-γ in whole lung; and IL-6, TNF-α and IL-1ß protein levels in BALF. CONCLUSION: Collectively, our results suggest that herbal decoction DSK is effective in protecting against allergic airway inflammation and remodelling by regulating anti-oxidant mechanisms. We postulate that DSK could be the potential therapeutic option for allergic asthma management.