An Analytical Study of Kalmegh (Andrographis Paniculata) and Kiratikta (Swertia Chirayita): An Economic Substitution for Metro Cities in Global Pandemic with Healthcare 4.0

Present Crisis of Pandemic and Indian Ecosystem

The COVID-19 pandemic has created a disturbance for the global health care system. Health organizations and institutions fighting infectious disease, supporting health workers, delivering social services, and protecting livelihoods have captured the world’s attention [1, 2, 3, 4, 5, 6, 7, 8]. Due to this pandemic challenges of access, safety, supply chain logistics and financial stress were faced by everyone like never before. The short-term implications of this global challenge are evident everywhere, but the long term consequences of the pandemic, how it will affect health and development institutions, government policies, occupations, and priorities are still difficult to imagine [9].

As modern science is evidence based science and depends upon authentic research, it is difficult to develop treatment protocol for Covid-19 in such a short duration and without proper authentic research which takes its stipulated time. In the case of conventional medicine, this inevitable dilemma between medical research and clinical medicine has been resolved by the parallel development of the pragmatic standard of care guidelines for clinical practice while at the same time pursuing rigorous research protocols to generate higher levels of evidence.

Global Scenario of Healthcare

Today Global health depends upon 6 major issues- Pandemics, environmental factors, economic disparities, political factors, non-communicable disease and animal health food sourcing and supply. And there are three challenges i.e. building medical capacity, increasing access to medicines and improving medical information [10].

There is a need for a holistic approach. Focus should be targeted at changing lifestyles so that everyone can live a healthier life. Health care leaders worldwide can adopt 3 major initiatives. First one is Intervene at the intersection of health and lifestyle, second one is Transition from volume to value and the last one is Interoperability in the digital age. Basic need is the power of integration which can easily help to eradicate major health issues all over the world and turn our planet into a healthy one [11].

Allopathic Medicine and their Side Effects

There are a variety of modern medicines available to fight the germs in different ways, either to kill it or to stop its production. But neither of the treatments focuses on prevention, and treatment is always disease specific not patient oriented i.e. it focuses on the part, not complete health. So, allopathic treatment is not having a holistic approach to treat something in the best way. The disease might appear again, leading to expenses of both money and time [12, 13].

Indian Vedic Life Style and Science of Ayurveda

Ayurveda is an age-old science, comes from the ancient Vedic tradition of India. It is known as the upveda of the Atharva Veda. It is understood as the science of life. It is a study of life based on the direct experience of the Ayurveda Siddhant i.e. fundamental „laws of nature‟ that govern our world and that cannot be challenged. Ayurveda basically deals with areas such as Dravya (herbs), Ahara (diet), Vyayama ( exercise), Prakriti (individual constitutions) and most important are Yoga and _Swasthwrit_t (Preventive social medicine). So treatment with a holistic approach is possible through Ayurveda only [14].

Kalmegh (Andrographis paniculata)

Andrographis paniculata (Burm. f.)Wall.ex Nees belongs to the family Acanthaceae commonly known as King of Bitters. It is used for centuries in Asia as ethno medicine for the treatment of various ailments such as dyspepsia, diarrhea, dysentery, influenza, respiratory infections, malaria, and is used as an antidote for snake-bite and poisonous stings of some insects [16]. This herb is used by the tribals of Tamilnadu, India, to treat different diseases like dysmenorrhea, leucorrhoea, prenatal and postnatal care, intestinal worm infestation, eczema, leucoderma, malaria, jaundice, gonorrhea, and general disorders like wounds, cuts, boils, and skin diseases [17]. In Malaysia, its decoction is used to treat cancer, hypertension, diabetes, malaria, common cold, and snakebite. In traditional Chinese medicine, it is seen as the cold-property herb used to rid of the body heat and fever and to expel toxins from the body [18]. In Ayurveda_, Kalmegh_ is indicated especially in liver disorders and fever, skin disease, intestinal worm infestation as well. A. paniculata is an important constituent of at least 26 formulas in Indian pharmacopeia and described in American and British pharmacopoeias as well [19].

Kiratatikta (Swertia chirayita)

S. chirayita, commonly known as “Chirayta” belongs to the family of Gentianaceae is an important plant for various herbal remedies. It is very commonly used by local people as a remedy for various disorders like hepatitis, fever, vomiting, and indigestion. Decoction of Chirayta is used traditionally, as hepatoprotective, anthelmintic, antimalarial, antifungal, and antibacterial, cardiac stimulant, anti-fatigue, anti- inflammatory, anti-aging, and antidiarrheal. It is beneficial for the vital organs like liver and heart, it lowers blood sugar and blood pressure as well [5]. Ayurveda medicine system state extensive range of indications of Kiratatikta like chronic fever, malaria, anemia, bronchial asthma, liver disorder, dyspepsia, gastritis, ulcers, constipation, skin diseases, intestinal worms, epilepsy, and certain types of mental disorders, and Prameha (diabetes) [20]. It increases secretions of bile and purifies blood. Herbal formulations such as Ayush-64, Sudarshan churna, Sudarshan ghan vati, Mensturyl syrup, Diabecon, and ointment Melicon V contain S. chirayita extract [21]. S. chirayita is mentioned in American and British pharmacopeias in the forms of infusions and tinctures. It’s extract shows a wide range of pharmacological activities, such as antimicrobial, anti-neoplastic, anti- diabetic, antioxidant, and anti-inflammatory activities [22].

In respect to Ayurveda

In, Ayurveda, pharmacological actions of any drugs are based on their Rasa panchaka (properties and actions) i.e. Rasa (Taste), Guna (physical property), Virya (potency), Vipaka (post metabolism test) and karma (therapeutic action). According to Ayurvedic Pharmacopeia of India, the properties and actions of Kalmegha and Kiratatikta are listed in (Table-1). We found all the properties are similar except for their potency and some difference in their actions [29, 30].

Most of the actions and uses of both the drugs are similar as presented (Table-2) [20]. In “Pharmacognosy of Ayurvedic drugs of Travancore, the cochine’’ Andrographis paniculata is described for Kiratatikta.

Ethno-Medicinal Uses

Kalmegh is used commonly by the ethnics of Kerala, Tamilnadu, and other southern parts of India while Kiratatikta is used in Uttarakhand, Sikkim and other Himalayan regions for similar therapeutic uses. The preference for one drug over the other is based on their availability in a particular region (Table 3).

Pharmacological Actions

On reviewing several research papers we have found that both the drugs A. paniculata and Swertia chirayita are very important medicines. Both of these drugs perform various pharmacological actions such as antimicrobial, anti-malarial, anti-inflammatory, anti-oxidant, immune-stimulant, anti- diabetic, anti-angiogenic, hepato-renal protective, and anti- toxic [19] (Table 4).

Methods

For the entire study of both the drugs i.e. S. chirayita and A. paniculata, various aspects were considered. First of all, the team did a critical review of ancient literature along with modern literature. Data compiled and presented here were obtained through Ayurvedic texts like Chikitsa & Samhita Granthas, Nighantus, and other authentic books, E-resources like Science Direct, Pubmed, Google, and research papers up to September 2021.

Secondly analytical study has been done in the laboratory for organoleptic, physicochemical and phytochemical analysis. Samples were collected from their native place of plants. The samples of Kiratatikta were collected from high hills of Dhanolti and Kalamegha from Dev Samskriti Vishwavidyalaya, Shantikunj, Haridwar, and Uttarakhand. Collected samples of both herbs were kept for drying by keeping them between the folds of old newspapers. The dried specimens were then pasted on the herbarium sheets of standard size and proper labeling was done and was certified from Botanical Survey of India, Dehradun. Organoleptic Study: All the collected samples were dried and powdered for further study. The powdered sample of both drugs observed with naked eye & magnifying lens, to analyze different organoleptic features i.e. colour, odour, taste, and appearance were recorded [29]. Determination of pH Value: The pH value of an aqueous liquid may be defined as the common logarithm of the reciprocal of the hydrogen ion concentration expressed in grams per liter, the pH of both samples was measured by using a digital pH meter. Determination of Different Soluble Extract: 5 g coarse powder of sample drug macerated with 100 ml solvent, shaking frequently for six hours and allowed to stand for eighteen hours after that it was filtered, filtrate kept to dry in a tarred flat bottomed shallow dish. The percentage of solvent-soluble extract with reference to the drugs which are already dried in air is calculated. Determination of extract in different solvent like Aqueous, alcohol and Petroleum Ether was done in the same manner as mentioned above. Determination of Total Ash: Total amount of material remaining after ignition is measured through the total ash method. Both physiological ash which is derived from the plant tissue itself and non-physiological ash which is the residue of the extraneous matter (e.g. sand and soil) adhering to the plant surface are measured during the process. Silica Crucible was cleaned, dried well, labeled with glass pencils and then weighed to constant weight. 5 gm of powdered drug sample put in the Silica crucible. The drug was spread evenly into a thin layer. This crucible was placed in a muffle furnace and ignited at a temperature of 450°C for about 6 hrs or more until the ash was totally free from Carbon. The crucible containing the ash was allowed to be cooled in desiccators and subsequently weighed to constant weight. Calculation of ash with reference to the drug (which must be air dried) is performed. Determination of Acid Insoluble Ash: Acid insoluble Ash value was determined as per Ayurvedic Pharmacopoeia of India, 2008. Boiled the total ash, with 25 ml of 2M hydrochloric acid for 5 minutes, collected the insoluble matter in a Gooch crucible or on an ash less filter paper, washed with hot water, ignited, cool in a desiccator and weighed. Calculated the percentage of acid - insoluble ash with reference to the air - dried drug. Water-soluble Ash: Water – soluble ash value determined as per Ayurvedic Pharmacopoeia of India, 2008. Boiled the total ash for 5 minutes with 25 ml of water; collected the insoluble matter in a Gooch„s Crucible or on an ash less filter paper, washed with hot water and ignited for 15 minutes at a temperature not exceeding 450 C. It was subtracted (insoluble matter) from the weight of the ash; the difference in weight represented the water-soluble ash. Phytochemical Study: Freshly prepared extracts of both sample drugs were used for different tests to know the availability of different active phytochemicals as follows: Fehling solution test for Carbohydrates, Mayer reagent test for alkaloids, Biuret Test for amino acids and proteins, Foam test for saponins, Borntragor’s Test for glycosides, Phenolic Test for phenolic compounds, Salkowaski test for steroids, FeCl3 test for Tannins, Iodine test for starch, Test for Flavonoid, Test for Terpenoids.

Component Collection Data

• Collection of samples: The samples of Kiratatikta were collected from high hills of Dhanolti and Kalmegh_a from Dev Sanskriti Vishwavidyalaya, Shantikunj, Haridwar, Uttrakhand. The specimen of Kalmegha was collected in the last of September and _Kiratatikta was in the mid of September.
• Other materials: Magnifying Lens, measuring tape for organoleptic study. Eosin, Ferric chloride, Naphthol, Iodine, Sudan red III and Ethanol. All the analytical procedures were done in Pharmacognosy labs of GS Ayurveda Medical College (Figure 1).

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The flowchart briefly depicts the methodology of our research work which was broadly divided into two parts i.e. review study and analytical study. In the analytical study reviewing organoleptic features, physical parameters and phytochemicals of both drugs samples, later study reviews the presence of ten Phytochemicals in different extracts of both the drugs. Physico-chemical study then calculates the value of the respective parameters on the basis of which comparative study between the two drugs is performed.

Organoleptic Analysis

On the basis of organoleptic analysis we find not much difference between A. paniculata and S. chirayita; there is difference found only in their color, as organoleptic features of both samples are given below in tabular form (Table 5).

Physicochemical Analysis

• Moisture Content of both the samples was determined and it was found to be least in Kalamegha i.e. 8.70% while highest in sample of Kiratatikta i.e. 9.52%.
• Total ash content was found to be 5.19% in the sample of Kiratatikta and in the sample of Kalamegha is 8.62%. Acid insoluble ash was found to be lower in the sample of Kiratatikta 0.98% than in the sample of Kalamegha 1.72%. Water soluble Ash was also found lower in samples of Kiratatikta 1.24% than in samples of Kalamegha 3.42%.
• It was observed that values of alcohol soluble extract and water soluble extract were higher in samples of Kiratatikta i.e. respectively, 15.15% and 15.98% and found to be least in Kalamegha respectively 10.76% and 13.55% (Table 6).

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Here the blue bars give the values of A. paniculata and the yellow one show the data of S.chirayita. Here we can clearly see that except for the pH, total ash and acid insoluble ash the other values do not vary much. The difference in pH can be overcome by taking complementary drugs with desirable pH. Overall the study shows that A. paniculata can be a very good substitute for S. chirayita (Figures 2 & 3).

Total ash, water soluble ash, and acid insoluble ash were found higher in Andrographis paniculata in comparison to Swertia chirayita, indicating that the Andrographis paniculata contains more minerals. The presence of polar chemicals in Swertia chirayita indicates its greater alcohol and aqueous extractive values.

Qualitative Phytochemical Analysis

Phytochemical Study: Freshly prepared extracts of both sample drugs were used for different tests to know the availability of different active phytochemicals as follows.

• Carbohydrates: Fehling solution test showed the presence of carbohydrates in aqueous extract but not in alcohol extract and in petroleum ether extract.
• Alkaloid: In both samples, Mayer reagent test showed the presence of alkaloids in all extract i.e. aqueous, alcoholic and petroleum ether.
• Amino acids: Biuret Test showed the presence of amino acids in aqueous extract but not in Alcoholic and Petroleum ether extract of Kiratatikta and Kalamegha.
• Proteins: In both the samples, Biuret Test showed the presence of proteins in aqueous extract but not in Alcoholic extract and petroleum ether extract.
• Saponin: In both the samples, Foam test showed the presence of saponins in Aqueous extract and in alcoholic extract but not in petroleum ether extract.
• Glycosides: In both the sample, Borntragor’s Test showed presence of glycosides in the aqueous extract but not in Alcoholic and petroleum ether extracts.
• Phenolic Compounds: In sample of Kalamegha, Phenolic Test showed presence of phenolic compounds in aqueous and alcohol extracts but not in petroleum ether extracts while in sample of Kiratatikta, it showed presence of phenolic compounds in alcoholic extract but absent in petroleum ether and aqueous extract.
• Test for Steroids: In both the samples, Salkowaski test showed the presence of steroids in all extracts i.e. in aqueous, petroleum ether and in alcoholic extract.
• Test for Tannins: In Kalamegha sample, FeCl3 test showed presence of Tannins in aqueous extract and in alcoholic extract but absent in petroleum ether extract while in sample of Kiratatikta, it showed presence of Tannins in alcoholic extract but absent in aqueous extract and petroleum ether extract.
• Test for Starch: In both the samples, Iodine test showed presence of starch in the aqueous extract but absent in alcoholic and petroleum ether extracts.
• Test for Flavonoid: In both the samples, presence of flavonoids in all extracts i.e. aqueous extract, petroleum ether extract and alcoholic extract.
• Test for Terpenoids: In both the samples, Terpenoids test showed the presence of Terpenoids in alcoholic extract and petroleum ether extract but absent in Aqueous extract [30] (Table 7) (Figure 4).

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The above figure represents the comparison of respective phytochemicals present in the Aqueous medium for A. paniculata and S. chirayita. All the major phytochemicals are common between A. paniculata and S. chirayita except for the absence of phenolic compounds in S. chirayita and absence of terpenoids in both the plants.

Out of the total ten phytochemicals studied, nine (carbohydrates, alkaloids, proteins, saponins, glycosides, phenolic compounds, steroids, tannins, and flavonoids) were found in Andrographis paniculata (aqueous extract) and eight (carbohydrates, alkaloids, proteins, saponins, glycosides, phenolic compounds, steroids, tannins, and flavonoids) in Swertia chirayita (aqueous extract) that showed the possibility of broad spectrum activities of Andrographis paniculata as compared with Swertia chirayita. Phytochemicals studied in Alcoholic extracts of the comparative plants show the absence of two major phytochemicals i.e. proteins and glycosides. Again it shows the similarities between A.paniculata and S.chirayita (Figure 5).

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The last figure gives the data of phytochemicals present in the petroleum ether extracts of A. paniculata and S. chirayita. The least number of phytochemicals are present in the petrol extracts of the respective plants in comparison to their alcoholic and aqueous extracts. However again the phytochemicals present are similar for both the studied plants except for the absence of alkaloids in A. paniculata (Figure 6).

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Carbohydrates, steroids, flavonoids, and terpenoids were found in petroleum ether extracts of Andrographis paniculata and Swertia chirayita. Furthermore, alkaloids were exclusively found in the Swertia chirayita extract. Proteins, saponins, glycosides, phenolic compounds, and tannins, on the other hand, were not discovered in extracts.

Future Research Directions and Limitations

Future Research Directions:

• There is a need for holistic conservation of both the medicinal plants through the organic cultivation or micro propagation methods.
• The molecular pathways, cellular signaling, and genomic interactions of specific active constituents may be worked out through the application of cheminformatics, proteogenomic, and network pharmacological analysis.
• The synthetic analogs of these active chemical constituents may be further explored for drug-like properties.
• To establish the efficacy of both S. chirayita and A. paniculata, comparative clinical trials must be performed.

Limitations

This work did not analyze quantitative data of phytochemicals. In all probability it’s pivotal to perform the comparative critical study of S. chirayita and A. paniculata in order to prove their vitality. Comprehensive comparative studies may also be conducted with other species of Acanthaceae and Gentianaceae families.

Novelties

• Critical Comparative study of two herbs having almost similar properties.
• The manuscript discusses strengths & limitations for both the herbs.
• The presented work discusses why A. paniculata should be used as a substitute for S. chirayita.
• This study has a more practical approach and application which can benefit a common person also.
• Ethically, the manuscript motivates audiences to reduce consumption of Kiratatikta and thus prolonging the extinction.

Scope of the Study

The study shows the uprightness of indigenous knowledge of medicines. It also encourages us to dwell deeper in the ocean of natural herbs and traditional medicinal systems. This study will provide us a better replacement for Chirayta as it is an endangered herb. Also it opens up the gates for the discovery and development of more such drugs which need to be authenticated as substitutes for the traditional drugs which now are on the verge of extinction. Ethically it will lead to reduced consumption of Kiratatikta by us humans, prolonging its extinction hopefully for forever.

Role of Authors

Dr. Bhavna Singh acted as team leader and coordinated among all co-authors. She prepared the topic introduction and background study; also contributed to experiments. Rohit Rastogi prepared the structure of the manuscript and ensured the quality of the content along with all co-authors. Dr. Lalit Raj Singh and Dr. Ankur Singhal did the experimental Analysis and along with concluding remarks. Ms. Richa Singh has compiled the literature survey along with graphical Representations.

Ethical Certification

The experiments don’t include any human related experiments and no ethical violation has been made. Though the authors performed lab experiments with a comparative analytical study of two herbs i.e. S. chirayita and Andrographis paniculata, it doesn’t violate any health related measures.