Relationship between homoeopathic pharmacy and materia medica: an attempt at filling the lacuna in the modus operandi of homoeopathy

Padmesh Goyal

ABSTRACT
The main aim of this observational and correlational study was to relate the symptoms of the plant drugs with the clinical and experimental data present on the various active compounds present in the homoeopathic formulation of the drug. The data on active compounds and identification was collected from the Homoeopathic Pharmacopoeia’s and mass spectrometry, chromatographic studies of the plant extract.

INTRODUCTION
Since many years, questions have been raised regarding the action and efficacy of homoeopathic medicines, how they act and what biochemical changes take place; but by means of this article we attempt to find out the possible cell pathways involved in the pathophysiological action of the homoeopathic mother tinctures by diving into the vast knowledge of homoeopathic pharmacy with reference to the Homeopathic Pharmacopoeia of the United States (HPUS) and Homoeopathic Pharmacopoeia of India (HPI).

With help of this study, we aim to deduce the working of Chelidonium majus by studying the relationship between materia medica and its phytochemistry and introduce some possible explanations for symptoms as well as relationship of the drug.

MONOGRAPH OF C. majus ACCORDING TO HPI

• Botanical name: Chelidonium majus Linn.
• Family: Papaveraceae
• Part used: Whole plant

Description: An erect, perennial herb, 30 to 120 cm in height, loosely-branching with acrid saffron-colored juice. Leaves deeply pinnatifid, the segments ovate or obovate, crenate or lobed, sometimes 2 pinnatifid; glaucous beneath. Flowers in a small peduncled umbel, 6 to 8 mm across; sepals 2, petals 4, yellow in color, stamens many; ovary of 2 carpels, the style very short with 2-lobed stigmas; capsule, lined, 2.5 to 5 cm long, dehiscing from base upwards.

Mother tincture class (According to the old method): Class 1

ACTIVE COMPOUNDS OF Chelidonium majus

Phytochemical analysis of Chelidonium majus includes –

• Non-alkaloidal constituents: choline, histamine, tyramine, saponin
• Acids: chelidonic, malic, citric, caffeic (0.4%) ferulic (0.02%), p-coumaric (0.06%), gentisic and p-hydroxybenzoic acids
• Hydroxycinnamic acid derivates: (-)-2-(E)-caffeoyl-D-glyceric acid, (-)-4-(E)-caffeoyl-L-threonic acid, (-)-(2)-(E)-coffeoyl threonic acid lactone, (+)-(E)-caffeoyl-L-malic acid
• Flavonoids: rutin, quercetin, luteolin, hyperoside
• Phenyl carboxylic acids: gallic acid, chlorogenic acid
• Unsaturated fatty acids: linoleic acid, oleic acid
• Trace amounts of tannins, carotenoids and minerals
• Alkaloids: Alkaloids isolated from C. majus include isoquinoline, aporphine, and other types of alkaloids.

Various types of alkaloids include:

MS-TOF(mass spectrometry time of flight) analyses of aqueous ethanol C. majus (aerial plant) extracts revealed the presence of 12 alkaloids. The identities of chelidonine, sanguinarine, and chelerythrine were confirmed with available reference standards. Tentative identification of other alkaloids was performed by comparison of their chromatographic retention times and detected m/z values with literature data.

• Isoquinoline alkaloids
  1. Aporphine alkaloids
  2. Benzylisoquinoline alkaloids
     1. Protopine
     2. Protoberberine

• Benzophenanthridine

• Other alkaloids

Major alkaloids along with their references:

S. No.	Name with reference	Part of plant
Class	Protopine alkaloids
1.	Protopine (Kadan et al. (1990), Kim et al. (1999))	Whole plant
2.	Cryptopine (Seger et al. (2004), Zhao et al. (2020))	Whole plant
Class	Protoberberine alkaloids
1.	Berberine (Bugatti et al. (1987), Zhao et al. (2020), Warowicka et al. (2021))	Whole plant, latex
2.	Jatrorrhizine (Yang et al. (2017), Yang et al. (2024b))	Whole plant
3.	Columbamine (Yang et al. (2017), Yang et al. (2024b))	Whole plant
4.	Corysamine (Golkiewicz and Gadzikowska (1999), Zhao et al. (2020))	Whole plant
5.	Coptisine (Sárközi et al. (2006), Zhao et al. (2020), Warowicka et al. (2021))	Whole plant, latex
Class	Benzophenanthrine quaternary amine alkaloids
1.	Chelerythrine (Bugatti et al. (1987), Warowicka et al. (2019), Zhao et al. (2020))	Whole plant, latex
2.	Sanguinarine (Kaczmarek and Malek (1959), Warowicka et al. (2019), Zhao et al. (2020))	Whole plant, latex
Class	Hexahydrobenzophenthridine alkaloids
1.	Chelidonine (Bugatti et al. (1987), Zhao et al. (2020), Warowicka et al. (2021))	Whole plant, latex
2.	Chelamine (Slavík and Slavíková (1977), Táborská et al. (1994))	Whole plant
3.	Chelamidine (Slavík and Slavíková (1977), Táborská et al. (1994))	Whole plant
Class	Dihydrobenzophen-anthridine alkaloids
1.	Dihydrochelerythrine (Kadan et al. (1990), Oechslin et al. (1991))	Whole plant
2.	Dihydrosanguinarine (Slavík and Slavíková (1977), Kadan et al. (1990))	Whole plant
3.	8- Hydroxydihydrosanguinarine (Zuo et al. (2008))	Aerial part
4.	8-Hydroxydihydrochelerythrine (Zuo et al. (2008))	Aerial part

RELATIONSHIP BETWEEN MATERIA MEDICA AND ACTIVE COMPOUNDS OF THE DRUG
According to Physiological materia medica by Dr. Burt, Chelidonium acts on the liver through the pneumogastric nerve, produces congestion and active inflammation of the liver, jaundice, with nausea and bitter vomiting. Arrest of secretory functions from over – stimulation or obstruction of hepatic ducts, with white stools, or watery, with jaundice; urine brown or yellow, and loaded with bile.

Jaundice, congestion, and inflammation of the liver are certainly caused by this remedy; and it has made many brilliant cures of jaundice in acute and chronic hepatitis. Several cases of biliary calculi have been cured with large doses of Chelidonium.

Chelidonium produces, through pneumogastric nerve, hyperemia, inflammation, and hepatization of the lungs. We have catarrhal inflammation of the mucous membrane of the trachea and bronchi, especially with hepatic symptoms. (Bilious catarrh.)

MIND –

Forgetful, absent minded (Clarke’s Materia medica)

Great absence of mind, forgets what she wants to do or has done (Hering’s Materia medica)

Very forgetful as to what she was to do or had done. On going into another room to get a book, he had to stop and think several minutes for what purpose he had come for (second day), Absence of mind; he forgot to put on his stockings; when shaving, he rose from his chair before he had shaved his lips and chin (third day) (T.F. Allen’s Encyclopedia)

Possible mechanism – 8-Hydroxydihydrochelerythrine and 8- Hydroxydihydrosanguinarine, isolated from C. majus, exhibit strong inhibitory activity against acetylcholinesterase. They slow down the breakdown of acetylcholine and increase its levels in the brain (Cho et al., 2006). Decreased levels of acetylcholine are a key factor in the onset of Alzheimer’s disease. Therefore, Chelidonium can be suggested as an alternative to anti-dementia drugs.

MOUTH – Bad odor from the mouth (Hering’s Materia medica) (Clarke’s Materia medica)

Possible mechanism with clinical trials – Chelerythrine exhibits a strong antibacterial effect on Streptococcus mutans, the main caries-causing bacterium in the oral cavity. It effectively reduces the adhesion ability of S. mutans, suggesting its potential use as a preventative treatment for dental caries (Chen et al., 2011).

Boulwere et al. (1985): The C. majus alkaloids sanguinarine and chelerythrine were found effective in the control of the production of bacterial sulphur compounds responsible for a halitosis and of lowering the population of anaerobic bacteria, who produce volatile sulphur compounds or those which are capable of covalently trapping sulphur leading to bad breath.

THROAT – Tonsillitis:

Throat, Inflammation, sore throat; Tonsils – Chel (1) – Complete repertory

Throat, Inflammation, Tonsils – Chel (1) – Kent’s repertory

Experimental evidence – It has been demonstrated that C. majus improved overall immunity and decreased incidence of recurrences of tonsillitis in children (Khmel’nitskaia et al., 1998).

LIVER – It includes hepatocellular carcinoma as well as other symptoms such as liver fibrosis, hepatitis, gall stones, etc. In various studies, C. majus extract has shown hepatotoxic effects in large doses in healthy individuals which corresponds with Dr. Hahnemann’s principles of ‘Similia Similibus Curanter’, suggesting that these mechanisms might also be responsible for therapeutic effects of chelidonium in liver complaints.

Hepatotoxic effects – The alkaloids found in C. majus, including chelidonine, sanguinarine, berberine, coptisine, and chelerythrine, either alone or in combination, possess potential toxicity (Benninger et al., 1999). The metabolism of chelidonine was studied in a human liver microsomal model, revealing two demethylated metabolites containing phenolic hydroxyl groups after incubation with liver microsomes. These hydroxyl groups are easily oxidized into quinone compounds, which can combine with glutathione to form quinone-sulfide, depleting glutathione in the liver and causing hepatotoxicity (Zhang et al., 2018).

Hepatocellular carcinoma:

Liver, Cancer – Chel (1) – Phatak’s repertory

Abdomen, Cancer, Liver – Chel (3) – Complete repertory

Possible mechanism – Experiments have demonstrated that CHLD (chelidonine) inhibits telomerase activity in HepG2 (a human liver cancer cell line that are used in research to study drug metabolism, hepatotoxicity, and other liver-related functions) cells by down-regulating the expression of human telomerase reverse transcriptase and inducing apoptosis (Noureini and Wink, 2009; Noureini et al., 2017). Chelerythrine upregulates the relative expression of Bax and Caspase-3 proteins and mRNA, decreases the relative expression of Bcl-XL protein and mRNA, prevents proliferation in HepG2 hepatoma cells, and ultimately induces apoptosis (Han and Zhu, 2016).

Hepatitis:

Hypochondria, Inflammation, Liver – Chel – Knerr repertory

Abdomen, Inflammation, Liver – Chel (3) – Kent repertory

Experimental evidence – Anti-hepatitis B virus activities of dihydrochelerythrine were demonstrated by Wu et al., 2007.

Symptoms associated with gall bladder

Gall bladder, Stones – Chel (2) – Phatak’s Repertory

Hypochondria, Liver, Gall stones – Chel – Knerr’s repertory

Experimental observation – Ardjah H, conducted a retrospective study for 6 months with 206 patients by giving them a daily dosage of a solid preparation containing 125 mg of hydroalcoholic extract corresponding to 0.675 mg of chelidonine and/or a liquid preparation 3 × 20 drops corresponding to 0.15 mg of chelidonine was given. Complaints related to gall stones or cholecystectomy such as bloating, flatulence, diarrhea or constipation, lasting abdominal pain, food intolerance, etc.  showed significant levels of amelioration. (Therapeutische Aspekte funktioneller Oberbauchbeschwerden bei Erkrankungen der Gallenwege. Fortschr Med 1991;109(suppl 115):2-8)

Other symptoms: Liver enlarged, indurated, sensitive on pressure. Fatty liver, border of which extends to navel, with icterus. Spasmodic pain in region of liver. (Hering)

Possible mechanisms – Note: These mechanisms have been currently studied using rat cell models only, their mechanism in actual human cells might differ from the original.

Chelerythrine interfered with the expression of TGF-β1, Smad4, and Smad7 proteins, further confirming its inhibitory effect on hepatic fibrosis in mice, associated with the TGF-β/ Smads signaling pathway (Li et al., 2018).

Chelidonine can regulate the mRNA and protein expression of genes related to the PI3K/Akt/mTOR pathway, affecting the expression of autophagy marker proteins LC3 and p62, preventing the activation of hepatic stellate cells, and inhibiting liver fibrosis (Li et al., 2021). It also inhibited the proliferation of TGF-β1-activated hepatic stellate cells, further demonstrating its potential to reverse liver fibrosis (Li et al., 2019).

STOMACH –

Stomach, Cancer – Chel (1) – Synthesis repertory

Stomach, Cancer – Chel (2) – Complete repertory

Possible mechanism – Chelerythrine can effectively induce apoptosis in human gastric cancer (BGC 823) cells (Zong and Liu, 2006). Chelidonine can induce SGC-7901 (a human gastric cancer cell line that is commonly used in research to study gastric cancer) M phase arrest and mitotic slippage in human gastric cancer cells by down-regulating the expression of BubR1, Cdk1 and cyclin B1 proteins (Qu et al., 2016).

ABDOMEN – Pain through the hypochondria, and in the right scapula. Spasmodic constriction of the umbilical region. Violent pressing spasmodic pain in the umbilical region, lasting only a second, but frequently returning. Pain in the left side of the abdomen near the umbilicus. Pain in intestines above umbilicus, with sensation of constriction transversely (after ten minutes). Pain above the umbilicus, as if the abdomen were constricted by a string (third day), Drawing pains in the walls of the abdomen. (T.F. Allen’s Encyclopedia)

Colic, with nausea and retraction of the navel. Pain across the umbilicus, as if the abdomen were constricted by a string, Spasmodic drawing pains in both inguinal regions. (Hering’s Guiding symptoms)

Possible mechanism – Chelidonine mitigates the occurrence of neuropathic pain by inhibiting the activation of PKC (protein kinase C) and spinal cord astrocytes (Chen et al., 2014). In addition, for chronic pain, the alkaloids in C. majus mainly induce central analgesia through a network mode of multiple target interventions, targeting SRC, AKT1, EGFR, CASP3, and MAPK3, resulting in anti-functional abdominal pain effects (Zhang et al., 2023).

SKIN –

Face, Eruptions, Herpes – Chel (1) – Synthesis repertory

Face, Eruptions, Herpes – Chel (1) – Kent’s repertory

Possible mechanism – Chelidonium may be used for effectively reducing HPV infection, and suppressing the expression of the viral oncogenes (E6, E7) at the mRNA and protein levels (Musidlak et al., 2022). CHE (Chelerythrine) can directly target the gB and gD glycoproteins on the surface of HSV-1, thereby inhibiting HSV-1 infection by preventing the binding of the virus to cells (Hu et al., 2023)

Alkaloid extract has shown antiviral efficacy against human adenoviruses type 5 and 12, herpes simplex virus, and RNA polio virus (Zuo et al., 2008; Horvath et al., 1983; Kery et al., 1987).

Relationship – Sanguinaria canadensis is comparable to Chelidonium majus (Clarke’s Materia medica) in various symptoms such as rheumatism of right ankle, complaints going from right to left, etc. which may be due to comparable levels of Benzophenanthrine quaternary amine alkaloids such as sanguinarine and chelerythrine as well as Protoberberine alkaloids compounds like berberine in both the plants.

Chelidonium is an antidote to as well as follows Bryonia alba, It is a close analogue in many symptoms; yellow tongue, swelling of liver (Clarke’s Materia medica)

Possible explanation – Cucurbitacins in Bryonia Alba have anti-inflammatory properties, while Chelidonium’s alkaloids like berberine and sanguinarine have detoxification and mild anti-inflammatory effects. Combining these could theoretically have a synergistic anti-inflammatory effect. Cucurbitacins and alkaloids (like chelidonine, sanguinarine) can both have effects on liver enzymes, possibly influencing their breakdown in the liver. If both tinctures are taken together, they could alter enzyme activity, either enhancing or inhibiting each other’s metabolism.

Area of research in further provings of Chelidonium majus –

LEUKEMIA

Havelek R team confirmed significant cytotoxicity of chelidonine and homochelidonine, effectively inducing leukemia cell death (Havelek et al., 2016). Chelerythrine and dihydrochelerythrine have been shown to arrest the cell cycle of HL-60 cells in the G1 phase, alter cell cycle distribution, and activate the mitochondrial apoptosis pathway, inducing apoptosis and necrosis in human leukemia HL-60 cells (Vrba et al., 2008).

Sanguinarine, berberine, and C. majus extracts have also exhibited significant cytotoxic and pro-apoptotic activities against hematopoietic cell lines HL-60, HL-60/MX1, HL-60/MX2, CCRF/CEM and CEM/C1, J45.01, and U266B, suggesting their potential utility in treating various types of leukemia (Och et al., 2019).

IMPOTENCY

The feeding of ethanolic extract of C. majus showed that it could combat the spermatotoxic effects to some extent in induced p-DAB induced carcinogenesis in mice. As benzophenanthridine alkaloids have marked nucleophilic properties, they might intercept the reactive metabolites; thereby preventing their attack on nucleophilic sites on DNA, and hence blocking adduct formation (Vavreckova et al., 1996 a, b).

The protective role of C. majus on sperm head could also be attributed to its regulatory effect on protein metabolism and repair activities in the germinal cells (Biswas and Khuda-Bukhsh, 2002).

CONCLUSION
The study of phytoconstituents of mother tinctures by application of HPLC(high performance liquid chromatography) and mass spectrometry can help us in understanding mechanism of action of the drug and its correlation with materia medica. It can introduce us to an entirely different method of studying materia medica. While this type of study is only limited to plant drugs with mother tincture usage, it may open possibilities of recording of completely new group of symptoms, although large number of experiments are required to prove this correlational evidence.

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Padmesh Goyal
4 BHMS HMCH Chandigarh
Email: padmesh16072002@gmail.com