AYURAKSHA, a prophylactic Ayurvedic immunity boosting kit reducing positivity percentage of IgG COVID-19 among frontline Indian Delhi police personnel: A non-randomized controlled intervention trial.

Objective: The world continues to face the COVID-19 crisis, and efforts are underway to integrate traditional medicine interventions for its effective management. The study aimed to determine the efficacy of the "AYURAKSHA" kit in terms of post-interventional percentage of COVID-19 IgG positivity, immunity levels, and quality of life (QoL) against COVID-19. Method: This was a non-randomized controlled, prospective intervention trial, done after the distribution of 80,000 AYURAKSHA kits (constituent of Sanshamani Vati, AYUSH Kadha, and Anu Taila) among Delhi police participants in India. Among 47,827 participants, the trial group (n = 101) was evaluated with the positivity percentage of IgG COVID-19 and Immune Status Questionnaire (ISQ) scores as a primary outcome and the WHO Quality of Life Brief Version (QOL BREF) scores along with hematological parameters as a secondary outcome in comparison to the control group (n = 71). Results: The data showed that the percentage of COVID-19 IgG positivity was significantly lower in the trial group (17.5 %) as compared to the control group (39.4 %, p = 0.003), indicating the lower risk (55.6%) of COVID-19 infection in the trial group. The decreased incidence (5.05%) and reduced mortality percentage (0.44%) of COVID-19 among Delhi police officers during peak times of the pandemic also corroborate our findings. The ISQ score and WHO-QOL BREF tool analysis showed the improved scores in the trial group when compared with the controls. Furthermore, no dysregulated blood profile and no increase in inflammation markers like C-reactive protein, erythrocyte sedimentation rate, Interleukin-6 (IL-6) were observed in the trial group. However, significantly enhanced (p = 0.027) IL-6 levels and random blood sugar levels were found in the control group (p = 0.032), compared to a trial group (p = 0.165) post-intervention. Importantly, the control group showed more significant (p = 0.0001) decline in lymphocyte subsets CD3+ (% change = 21.04), CD4+ (% change = 20.34) and CD8+ (% change = 21.54) levels than in trial group, confirming more severity of COVID-19 infection in the control group. Conclusion: The AYURAKSHA kit is associated with reduced COVID-19 positivity and with a better quality of life among the trial group. Hence, the study encourages in-depth research and future integration of traditional medicines for the prevention of the COVID-19 pandemic. Clinical trial registration: http://ctri.nic.in/, identifier: CTRI/2020/05/025171.

Neem (Azadirachta Indica A. Juss) Capsules for Prophylaxis of COVID-19 Infection: A Pilot, Double-Blind, Randomized Controlled Trial.

CONTEXT: SARS-CoV-2 is a global public-health concern. Interventions to prevent infection are urgently needed. The anti-inflammatory and antiviral effects of neem make it a potential agent for COVID-19 prophylaxis. OBJECTIVE: The study intended to evaluate the prophylactic effects of neem capsules for persons at high risk of COVID-19 infection due to contact with COVID-19 positive patients. DESIGN: The research team designed a prospective, randomized, double-blind, placebo-controlled, parallel-design study. SETTING: The study was conducted at a single center in India. PARTICIPANTS: Participants were 190 healthcare workers at the hospital or relatives of patients with COVID-19 infection. INTERVENTION: Of the 190 participants, 95 were in the intervention group and 95 in the control group. Participants received 50 mg of a proprietary, patent-pending, neem-leaf extract or a placebo orally in capsules, twice a day for 28 days. OUTCOME MEASURES: The number of individuals positive for COVID-19 between baseline and follow-up on day 56 was the primary outcome measure. Secondary measures included an evaluation of neem's safety and its effects on quality of life (QOL) and changes in biomarkers. RESULTS: The mean age of participants was 36.97 years, and 68.42% were male. Total 13 subjects tested positive during the study. All were asymptomatic. Of the 154 participants who completed the study per-protocol, 11 tested positive, 3 in the intervention group and 8 in the control group. The probability of COVID-19 infection in participants receiving the intervention was 0.45 times that of participants receiving the placebo, a relative risk of 0.45, with the effectiveness of the intervention being around 55%. Treatment-emergent adverse events (TEAEs) in both groups were minimal and were of grade 1 or 2 in severity. Biomarkers and QOL remained stable in both groups. CONCLUSIONS: The study found a reduced risk of COVID-19 infection in participants receiving neem capsules, which demonstrates its potential as a prophylactic treatment for the prevention of COVID-19 infection. The findings warrant further investigation in clinical trials.

Pharmacodynamic appraisal of wound-healing herbs of Sushruta Samhita.

Background: In Sushruta Samhita, various medicinal plants as single and compound formulations having Vrana-Shodhana (wound cleansing) and Vrana-Ropana (wound healing) potential are enumerated. There are no published data available on these wound-healing medicinal plants of Sushruta Samhita. The effectivee management of wound is necessary in the immunocompromised and chronic wounds patients as they take more time to heal. Aim: To review and systematically analyze wound-healing medicinal plants and their modus-operandi on the basis of pharmacodynamics attributes, i.e., Rasa (taste), Veerya (potency), and Vipaka (biotransformation) in the various stages of healing. Materials and methods: Review of Sushruta Samhita was done to gather wound-healing medicinal plants; pharmacodynamics attributes were gatherd from various Nighantus to understand their role in wound healing. The contemporary information about wound-healing mechanism was gathered from PubMed to interpitate the rational use of plants in the various stages of wound healing. Results: The study suggests that 43 medicinal plants have Vrana-Shodhana activity, 48 have Vrana-Ropana and 62 have both Vrana-Shodhana and Vrana-Ropana potential. Medicinal plants with Vrana-Shodhana category are having predominance of Katu (pungent), Tikta (bitter) and Kashaya (astriengent) Rasa. Plants under Vrana-Ropana are having Madhura, Kashaya Rasa (sweet taste), Madhura Vipaka (sweet biotransform) and Sheeta Veerya (cold potency). Conclusion: Plants having Tikta, Kashaya Rasa, Katu Vipaka, and Sheeta Veerya may be useful in the inflammatory stage, plants having Madhura, Kashaya Rasa and Sheeta Veerya may be useful in the prolifiratory stage and plants having Madhura Rasa, Sheeta Veerya, and Madhura Vipaka may be useful in the remodeling stage. The present review will help to give the directions to the researchers for the development of effective wound-healing medicines for wounds.

Pharmacological evaluation of Mallotus philippinensis (Lam.) Muell.-Arg. fruit hair extract for anti-inflammatory, analgesic and hypnotic activity.

OBJECTIVE: Recently, we observed wound healing activity of 50% ethanol extract of Mallotus philippinensis Muell. Arg (MP) fruit hairs extract (MPE). In several intestinal infections, localized inflammation is of common occurrence and hence we evaluated the anti-inflammatory, analgesic and hypnotic activity of MPE in different rat experimental models. MATERIALS AND METHODS: Anti-inflammatory activity was evaluated by carrageenan (acute) and turpentine oil induced formalin (subacute) induced paw edema and while granuloma pouch (subacute) in rats. Analgesic and hypnotic activity of MPE was undertaken by tail-flick, hot-plate, and acetic acid-induced writhing tests while pentobarbitone-induced hypnotic potentiation in rats. RESULTS: MPE at a dose of 200 mg/kg at 3 h after their administration showed inhibition of formalin-induced paw edema by 41.60% (P < 0.001) and carrageenan-induced paw edema by 55.30% (P < 0.001). After 7 days of treatments, MPE showed 38.0% (P < 0.001) inhibition against formalin-induced paw edema and reduced weight of turpentine-induced granuloma pouch by 29.6% (P < 0.01) and volume of exudates by 26.1% (P < 0.01), respectively. MPE (200 mg/kg) showed dose-dependent elevation in pain threshold and peak analgesic effect at 120 min as evidenced by increased latency period in tail flick method and increased reaction time in the hot-plate test while the reduction in the number of acetic acid-induced writhes by 45.7% (P < 0.001). The pentobarbitone-induced hypnosis model showed potentiation, as defined by increased duration of sleep in treated group rats as compared to control. CONCLUSION: Thus, the study revealed MPE is effective in reducing acute and subacute inflammation and showed effective and similar analgesic activity. This seemed to be safe in the treatment of pain and inflammation.

Mallotus philippinensis Muell. Arg fruit glandular hairs extract promotes wound healing on different wound model in rats.

BACKGROUND: Mallotus philippinensis Muell. Arg (MP, Euphorbiaceae) are widely distributed perennial shrub or small tree in tropical and subtropical region in outer Himalayas regions. Since, Mallotus philippinensis have been shown to have a number of medicinal values. Hence our present study was to investigate the healing potential of fruit extract in rat wound models. METHODS: The study includes acute toxicity and wound healing potential of 50% ethanol extract of MP fruit glandular hair (MPE). MPE (200 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound) and 22 days (excision wound). MPE was found safe when given to rats upto 10 times of optimal effective dose. Wound breaking strength (WBS) in Incision wound and rate of contraction, period of epithelization and scar area in Excision wound were evaluated. Granulation tissue free radicals (nitric oxide and lipid peroxidation), antioxidants (catalase, superoxide dismutase, and reduced glutathione), acute inflammatory marker (myeloperoxidase), connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid), and deep connective tissue histology were studied in Dead space wound. RESULTS: MPE significantly increased WBS and enhanced wound contraction, and decreased both epithelization period and scar area compared with control group. MPE was found to decrease free radicals (50.8 to 55.2%, P<0.001) and myeloperoxidase (44.0%, P<0.001) but enhanced antioxidants (41.1 to 54.5%, P<0.05 to P<0.001) and connective tissue markers (39.5 to 67.3%, P<0.05 to P<0.01). Histopathological evaluation revealed more density of collagen formation with minimal inflammatory cells in deeper tissues. CONCLUSION: Thus, the study revealed Mallotus philippinensis fruit hair extract, safe and effective in wound healing and the healing effects seemed to be due to decrease in free radical generated tissue damage, promoting effects on antioxidant status and faster collagen deposition as evidenced biochemically and histology.

Wound healing and antimicrobial activity of two classical formulations of Laghupanchamula in rats.

BACKGROUND: Wounds affect a large number of patients and seriously reduce the quality of life. The wound as a medical problem was first discussed by Maharshi Agnivesha in Agnivesha Samhita (later known as Charaka Samhita) as Vrana. Laghupanchamula denotes a combination of the roots of five herbs. However, in Ayurvedic classics, besides four common herbs viz. Kantakari, Brihati, Shalaparni and Prinshniparni, the fifth one is either Gokshura (LPG) or Eranda (LPE), and both formulations have been documented to have wound healing (Vrana) activity. OBJECTIVE: The present study was undertaken to determine the in vivo wound healing activity and in vitro antimicrobial activity of 50% ethanolic extract of Laghupanchamula containing Gokshura (LPGE) and Laghupanchamula containing Eranda (LPEE) in rats with acute toxicity in mice. MATERIALS AND METHODS: LPGE and LPEE (1000 mg/kg) was administered orally, once daily for 10 days (incision wound model) or for 24 days (excision wound model) in rats. LPGE and LPEE was studied for its in vitro antimicrobial and in vivo wound breaking strength (WBS) (incision model) and rate of contraction, period of epithelization and histology of skin (excision model). RESULTS AND CONCLUSION: LPGE and LPEE showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation and early epithelization period with low scar area indicating enhanced healing with histological evidence of more collagen formation in skin tissues. LPGE and LPEE also showed anti-bacterial activity and seemed to be safe, and use of both formulations in Laghupanchamula for their wound healing and anti-microbial activities is thus authenticated.

Analgesic and hypnotic activities of Laghupanchamula: A preclinical study.

BACKGROUND: In Ayurvedic classics, two types of Laghupanchamula -five plant roots (LP) have been mentioned containing four common plants viz. Kantakari, Brihati, Shalaparni, and Prinshniparni and the fifth plant is either Gokshura (LPG) or Eranda (LPE). LP has been documented to have Shothahara (anti-inflammatory), Shulanashka (analgesic), Jvarahara (antipyretic), and Rasayana (rejuvenator) activities. AIM: To evaluate the acute toxicity (in mice), analgesic and hypnotic activity (in rats) of 50% ethanolic extract of LPG (LPGE) and LPE (LPEE). MATERIALS AND METHODS: LPEG and LPEE were prepared separately by using 50% ethanol following the standard procedures. A graded dose (250, 500 and 1000 mg/kg) response study for both LPEE and LPGE was carried out for analgesic activity against rat tail flick response which indicated 500 mg/kg as the optimal effective analgesic dose. Hence, 500 mg/kg dose of LPEE and LPGE was used for hot plate test and acetic acid induced writhing model in analgesic activity and for evaluation of hypnotic activity. RESULTS: Both the extracts did not produce any acute toxicity in mice at single oral dose of 2.0 g/kg. Both LPGE and LPEE (250, 500, and 1000 mg/kg) showed dose-dependent elevation in pain threshold and peak analgesic effect at 60 min as evidenced by increased latency period in tail-flick method by 25.1-62.4% and 38.2-79.0% respectively. LPGE and LPEE (500 mg/kg) increased reaction time in hot-plate test at peak 60 min analgesic effect by 63.2 and 85.8% and reduction in the number of acetic acid-induced writhes by 55.9 and 65.8% respectively. Both potentiated pentobarbitone-induced hypnosis as indicated by increased duration of sleep in treated rats. CONCLUSION: The analgesic and hypnotic effects of LP formulations authenticate their uses in Ayurvedic system of Medicine for painful conditions.

Anti-inflammatory activity of two classical formulations of Laghupanchamula in rats.

BACKGROUND: Laghupanchamula denotes combinations of roots of five herbs. However, in Ayurvedic classics besides four common herbs viz. Kantakari, Brihati, Shaliparni, and Prinshniparni, the fifth one is either Gokshura (Laghupanchamula with Gokshura LPG) or Eranda (Laghupanchamula with Eranda LPE), and both formulations have been documented to have shothahara (anti-inflammatory) action. OBJECTIVES: The present study was undertaken to compare the anti-inflammatory activity of 50% ethanolic extract of LPG (LPGE) and LPE (LPEE) in rats and safety in mice. MATERIALS AND METHODS: LPGE and LPEE were given orally, administered either just before or 60 min before experiment on mice and for 7 days to rats. Paw edema was induced by carrageenan (acute) and formalin (sub-acute), whereas granuloma pouch (sub-acute) was induced by turpentine in rats. RESULTS: Both LPGE and LPEE (1.0 g/kg) at 3 h after their administration showed inhibition of formalin-induced paw edema by 46.2% and 44.3% (P < 0.001) and carrageenan-induced paw edema by 53.9% and 60.4% (P < 0.001), respectively. After 7 days of treatment, both LPGE and LPEE showed 26.3% (P < 0.01) and 32.5% (P < 0.05) inhibition, respectively, against formalin-induced paw edema, and reduced weight of turpentine-induced granuloma pouch by 42.8% and 36.1% (P < 0.001), and volume of exudates by 31.2% and 36.2% (P < 0.001), respectively. No acute toxicity was observed in mice even with a 10.0-g/kg dose of both extracts. CONCLUSION: LPGE and LPEE significantly reduced acute and sub-acute inflammation, and showed effective and similar anti-inflammatory activity. They seemed to be safe, and use of both formulations in the Laghupanchamula for their anti-inflammatory activity is, thus, authenticated.

Pharmacological evaluation of extracts of Hedychium spicatum (Ham-ex-Smith) rhizome.

Hedychium spicatum (Ham-ex-Smith), known as Shati in Ayurvedic classics, is documented for the treatment of cough, hiccough, fever and asthma. The present study includes the evaluation of aqueous and ethanolic extracts of the dried rhizome of H. spicatum for anti-histaminic and ulcer-protective activities in guinea pig (GP), anti-inflammatory and analgesic activities in rat and acute toxicity in mouse. The extracts were administered orally, daily as suspension, in 1% carboxymethyl cellulose either for 7 days in GP studies or 60 min before or just before experiment in rats and mice. An initial dose-dependent anti-histaminic action of both the extracts (100, 200 and 400 mg/kg) was performed against histamine-induced bronchospasm in GPs. The 200 mg/ kg dose of aqueous and ethanolic extracts was selected both in GP and rat for further studies. GPs treated with aqueous and ethanolic extracts showed gastric ulcer protection against histamine-induced gastric ulcer compared with the control group. Both the extracts also showed an anti-inflammatory effect against carrageenan-induced paw edema in rats from 1 h onwards, and this was maximum at 3 h. Analgesic effect was determined by using hot plate and tail flick tests in rats, and both the extracts at 200 mg/kg showed a significant increase in the latent period from 30 min onwards till 120 min of their study period. Both the extracts did not show any toxic effect like increased motor activity, salivation, clonic convulsion, coma and death in mice even at the 2000 mg/kg dose (nearly 10 times of the optimal effective dose), indicating the safety of the extracts. The result confirms the indigenous use of this plant in respiratory disorders.

A critical review on two types of Laghupanchamula.

A group of five roots of small plants i.e., Shalaparni, Prshniparni, Brhati, Kantakari and Gokshura or Eranda is known as Laghupanchamula under Mishraka Varga (group of drugs). It is used as such or with Mahat Panchamula i.e., Bilva, Gambhari, Shyonaka, Agnimantha and Patala, constituting Dashamula, a well recognized and popular Ayurvedic preparation or as an ingredient of different dosage forms. Classical texts of Ayurveda differs regarding components of this Mishraka Varga. Four out of five drugs of Laghupanchamula are similar in all the Ayurvedic texts, but either Gokshura or Eranda is considered as the fifth drug. So a comphrenesive review of Veda, Samhita Grantha, Cikitsa Grantha and Nighantus, with regards to synonyms, contents, Guna- Karma, origin of variation in contents and possible thought behind two kinds of Laghupanchamula, to throw light for rational use of either Eranda or Gokshura under Laghupanchamula was conducted. It was observed that both the traditions were in practice however Acharya Kashyapa and Ravigupta were in view of Eranda as a fifth drug of Laghupanchamula where as Acharya Charaka, Sushruta, Vagabhatta, Yogaratnakara and Chakradatta are in favour of Gokshura. Infact, the variation in content depends on the need i.e Dosha, Dushya and Vyadhi.