Difference between revisions of "Journal:Fertilization following pollination predominantly decreases phytocannabinoids accumulation and alters the accumulation of terpenoids in Cannabis inflorescences"

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==Introduction==
==Introduction==
''[[Cannabis sativa]]'' L. (''[[Cannabis]]'') has been known as a medicinal plant since ancient times.<ref>{{Cite journal |last=Bonini |first=Sara Anna |last2=Premoli |first2=Marika |last3=Tambaro |first3=Simone |last4=Kumar |first4=Amit |last5=Maccarinelli |first5=Giuseppina |last6=Memo |first6=Maurizio |last7=Mastinu |first7=Andrea |date=2018-12 |title=Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history |url=https://linkinghub.elsevier.com/retrieve/pii/S0378874118316611 |journal=Journal of Ethnopharmacology |language=en |volume=227 |pages=300–315 |doi=10.1016/j.jep.2018.09.004}}</ref> During the last two decades, many studies have added to the growing evidence for its therapeutic effects in a wide range of conditions such as neurodegenerative disorders<ref>{{Cite journal |last=Fernández-Ruiz |first=Javier |date=2019-05 |title=The biomedical challenge of neurodegenerative disorders: an opportunity for cannabinoid-based therapies to improve on the poor current therapeutic outcomes: Cannabinoids and neuroprotection |url=https://onlinelibrary.wiley.com/doi/10.1111/bph.14382 |journal=British Journal of Pharmacology |language=en |volume=176 |issue=10 |pages=1370–1383 |doi=10.1111/bph.14382 |pmc=PMC6487558 |pmid=29856067}}</ref><ref>{{Cite journal |last=Cassano |first=Tommaso |last2=Villani |first2=Rosanna |last3=Pace |first3=Lorenzo |last4=Carbone |first4=Antonio |last5=Bukke |first5=Vidyasagar Naik |last6=Orkisz |first6=Stanislaw |last7=Avolio |first7=Carlo |last8=Serviddio |first8=Gaetano |date=2020-03-06 |title=From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases |url=https://www.frontiersin.org/article/10.3389/fphar.2020.00124/full |journal=Frontiers in Pharmacology |volume=11 |pages=124 |doi=10.3389/fphar.2020.00124 |issn=1663-9812 |pmc=PMC7069528 |pmid=32210795}}</ref>, pain<ref>{{Citation |last=Starowicz |first=Katarzyna |last2=Finn |first2=David P. |date=2017 |title=Cannabinoids and Pain: Sites and Mechanisms of Action |url=https://linkinghub.elsevier.com/retrieve/pii/S1054358917300443 |work=Advances in Pharmacology |language=en |publisher=Elsevier |volume=80 |pages=437–475 |doi=10.1016/bs.apha.2017.05.003 |isbn=978-0-12-811232-8 |access-date=2021-11-24}}</ref>, epilepsy,<ref>{{Cite journal |last=Franco |first=Valentina |last2=Bialer |first2=Meir |last3=Perucca |first3=Emilio |date=2021-03 |title=Cannabidiol in the treatment of epilepsy: Current evidence and perspectives for further research |url=https://linkinghub.elsevier.com/retrieve/pii/S0028390820305104 |journal=Neuropharmacology |language=en |volume=185 |pages=108442 |doi=10.1016/j.neuropharm.2020.108442}}</ref> multiple sclerosis<ref>{{Cite journal |last=Rice |first=Jessica |last2=Cameron |first2=Michelle |date=2018-08 |title=Cannabinoids for Treatment of MS Symptoms: State of the Evidence |url=http://link.springer.com/10.1007/s11910-018-0859-x |journal=Current Neurology and Neuroscience Reports |language=en |volume=18 |issue=8 |pages=50 |doi=10.1007/s11910-018-0859-x |issn=1528-4042}}</ref>, and more.<ref>{{Cite journal |last=Gonçalves |first=Joana |last2=Rosado |first2=Tiago |last3=Soares |first3=Sofia |last4=Simão |first4=Ana |last5=Caramelo |first5=Débora |last6=Luís |first6=Ângelo |last7=Fernández |first7=Nicolás |last8=Barroso |first8=Mário |last9=Gallardo |first9=Eugenia |last10=Duarte |first10=Ana |date=2019-02-23 |title=Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination |url=http://www.mdpi.com/2305-6320/6/1/31 |journal=Medicines |language=en |volume=6 |issue=1 |pages=31 |doi=10.3390/medicines6010031 |issn=2305-6320 |pmc=PMC6473697 |pmid=30813390}}</ref> These therapeutic abilities have been attributed to the secondary metabolites biosynthesized in ''Cannabis''<ref>{{Cite journal |last=Andre |first=Christelle M. |last2=Hausman |first2=Jean-Francois |last3=Guerriero |first3=Gea |date=2016-02-04 |title=Cannabis sativa: The Plant of the Thousand and One Molecules |url=http://journal.frontiersin.org/Article/10.3389/fpls.2016.00019/abstract |journal=Frontiers in Plant Science |volume=7 |at=19 |doi=10.3389/fpls.2016.00019 |issn=1664-462X |pmc=PMC4740396 |pmid=26870049}}</ref>, with more than 500 different secondary metabolites having been identified.<ref>{{Cite journal |last=ElSohly |first=Mahmoud A. |last2=Slade |first2=Desmond |date=2005-12 |title=Chemical constituents of marijuana: The complex mixture of natural cannabinoids |url=https://linkinghub.elsevier.com/retrieve/pii/S002432050500891X |journal=Life Sciences |language=en |volume=78 |issue=5 |pages=539–548 |doi=10.1016/j.lfs.2005.09.011}}</ref><ref name=":0">{{Cite journal |last=Flores-Sanchez |first=Isvett Josefina |last2=Verpoorte |first2=Robert |date=2008-10 |title=Secondary metabolism in cannabis |url=http://link.springer.com/10.1007/s11101-008-9094-4 |journal=Phytochemistry Reviews |language=en |volume=7 |issue=3 |pages=615–639 |doi=10.1007/s11101-008-9094-4 |issn=1568-7767}}</ref> These metabolites belong to several groups of compounds, including [[Cannabinoid|phytocannabinoids]], [[terpenoid]]s, and [[flavonoid]]s.


To date, the most characterized are phytocannabinoids, lipophilic compounds made of isoprene units (five-carbon building blocks) (Hanuš et al., 2016), which are almost exclusive to the ''Cannabis'' plant. (Gülck and Møller, 2020) More than 140 different phytocannabinoids have been found to accumulate to various extents in glandular [[trichome]]s that are located in the aerial parts of the plant and mostly on the female flowers, which are arranged in a cluster on the stem of the [[inflorescence]].<ref>{{Cite journal |last=Hanuš |first=Lumír Ondřej |last2=Meyer |first2=Stefan Martin |last3=Muñoz |first3=Eduardo |last4=Taglialatela-Scafati |first4=Orazio |last5=Appendino |first5=Giovanni |date=2016 |title=Phytocannabinoids: a unified critical inventory |url=http://xlink.rsc.org/?DOI=C6NP00074F |journal=Natural Product Reports |language=en |volume=33 |issue=12 |pages=1357–1392 |doi=10.1039/C6NP00074F |issn=0265-0568}}</ref> Phytocannabinoids can be classified into several subclasses according to their chemical structure, including the [[Tetrahydrocannabinol|Δ<sup>9</sup>-tetrahydrocannabinol]] (THC) and [[cannabidiol]] (CBD) families, as well as [[cannabinol]] (CBN), [[cannabigerol]] (CBG), [[cannabichromene]] (CBC), and many others.<ref name=":0" /><ref>{{Cite journal |last=Berman |first=Paula |last2=Futoran |first2=Kate |last3=Lewitus |first3=Gil M. |last4=Mukha |first4=Dzmitry |last5=Benami |first5=Maya |last6=Shlomi |first6=Tomer |last7=Meiri |first7=David |date=2018-12 |title=A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis |url=http://www.nature.com/articles/s41598-018-32651-4 |journal=Scientific Reports |language=en |volume=8 |issue=1 |pages=14280 |doi=10.1038/s41598-018-32651-4 |issn=2045-2322 |pmc=PMC6155167 |pmid=30250104}}</ref>


Terpenoids, found in many other plants, represent a second large group of metabolites. These metabolites are closely related to phytocannabinoids, sharing the same isoprenoid precursor and built up by branched isoprene units.<ref>{{Cite journal |last=Booth |first=Judith K. |last2=Yuen |first2=Macaire M.S. |last3=Jancsik |first3=Sharon |last4=Madilao |first4=Lufiani L. |last5=Page |first5=Jonathan E. |last6=Bohlmann |first6=Jörg |date=2020-09 |title=Terpene Synthases and Terpene Variation in Cannabis sativa |url=https://academic.oup.com/plphys/article/184/1/130-147/6117797 |journal=Plant Physiology |language=en |volume=184 |issue=1 |pages=130–147 |doi=10.1104/pp.20.00593 |issn=0032-0889 |pmc=PMC7479917 |pmid=32591428}}</ref> Terpenoids are responsible for the fragrance and taste of the plant and are suggested to also have defensive roles. They may also contribute to the therapeutic effects attributed to ''Cannabis''.<ref>{{Citation |last=Russo |first=Ethan B. |last2=Marcu |first2=Jahan |date=2017 |title=Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads |url=https://linkinghub.elsevier.com/retrieve/pii/S1054358917300273 |work=Advances in Pharmacology |language=en |publisher=Elsevier |volume=80 |pages=67–134 |doi=10.1016/bs.apha.2017.03.004 |isbn=978-0-12-811232-8 |access-date=2021-11-24}}</ref>
Another group of metabolites worth mentioning is flavonoids. Among this group, which is widespread in the plant kingdom, there are three specific prenylated flavonoids, termed Cannflavins A, B, and C, which are unique to ''Cannabis'' and show potent anti-inflammatory abilities.<ref>{{Cite journal |last=Radwan |first=Mohamed M. |last2=ElSohly |first2=Mahmoud A. |last3=Slade |first3=Desmond |last4=Ahmed |first4=Safwat A. |last5=Wilson |first5=Lisa |last6=El-Alfy |first6=Abir T. |last7=Khan |first7=Ikhlas A. |last8=Ross |first8=Samir A. |date=2008-10 |title=Non-cannabinoid constituents from a high potency Cannabis sativa variety |url=https://linkinghub.elsevier.com/retrieve/pii/S0031942208003518 |journal=Phytochemistry |language=en |volume=69 |issue=14 |pages=2627–2633 |doi=10.1016/j.phytochem.2008.07.010 |pmc=PMC4888767 |pmid=18774146}}</ref><ref>{{Cite journal |last=Rea |first=Kevin A |last2=Casaretto |first2=José A. |last3=Al-Abdul-Wahid |first3=M. Sameer |last4=Sukumaran |first4=Arjun |last5=Geddes-McAlister |first5=Jennifer |last6=Rothstein |first6=Steven J. |last7=Akhtar |first7=Tariq A. |date=2019-08 |title=Biosynthesis of cannflavins A and B from Cannabis sativa L |url=https://linkinghub.elsevier.com/retrieve/pii/S0031942218303819 |journal=Phytochemistry |language=en |volume=164 |pages=162–171 |doi=10.1016/j.phytochem.2019.05.009}}</ref><ref>{{Cite journal |last=Erridge |first=Simon |last2=Mangal |first2=Nagina |last3=Salazar |first3=Oliver |last4=Pacchetti |first4=Barbara |last5=Sodergren |first5=Mikael H. |date=2020-10 |title=Cannflavins – From plant to patient: A scoping review |url=https://linkinghub.elsevier.com/retrieve/pii/S0367326X2030294X |journal=Fitoterapia |language=en |volume=146 |pages=104712 |doi=10.1016/j.fitote.2020.104712}}</ref>





Revision as of 22:35, 24 November 2021

Full article title Fertilization following pollination predominantly decreases phytocannabinoids accumulation and alters the accumulation of terpenoids in Cannabis inflorescences
Journal Frontiers in Plant Science
Author(s) Feder, Carni L.; Cohen, Oded; Shapira, Anna; Katzir, Itay; Peer, Reut; Guberman, Ohad; Procaccia, Shiri; Berman, Paula; Flaishman, Moshe; Meiri, David
Author affiliation(s) Technion-Israel Institute of Technology, Agricultural Research Organization of Israel
Primary contact Email: dmeiri at technion dot ac dot il
Editors Taglialatela-Scafati, Orazio
Year published 2021
Volume and issue 12
Article # 753847
DOI 10.3389/fpls.2021.753847
ISSN 1664-462X
Distribution license Creative Commons Attribution 4.0 International
Website https://www.frontiersin.org/articles/10.3389/fpls.2021.753847/full
Download https://www.frontiersin.org/articles/10.3389/fpls.2021.753847/pdf (PDF)

Abstract

Over the last few decades, a growing body of evidence has increasingly showed the therapeutic capabilities of Cannabis plants. These capabilities have been attributed to the specialized secondary metabolites stored in the glandular trichomes of female inflorescences, mainly phytocannabinoids and terpenoids. The accumulation of these metabolites in the flower is versatile and influenced by a largely unknown regulation system, attributed to genetic, developmental, and environmental factors. As Cannabis is a dioecious plant, one main factor is fertilization after successful pollination. Fertilized flowers are considerably less potent, likely due to changes in the contents of phytocannabinoids and terpenoids.

This study examined the effect of fertilization on metabolite composition by crossbreeding Δ9-tetrahydrocannabinol (THC)- or cannabidiol (CBD)-rich female plants with different male plants: THC-rich plants, CBD-rich plants, or the original female plant induced to develop male pollen sacs. We used advanced analytical methods to assess the phytocannabinoid and terpenoid content, including a newly developed semi-quantitative analysis for terpenoids without analytical standards.

We found that fertilization significantly decreased phytocannabinoid content. For terpenoids, the subgroup of monoterpenoids had similar trends to the phytocannabinoids, proposing both are commonly regulated in the plant. The sesquiterpenoids remained unchanged in the THC-rich female plants and had a trend of decreasing in the CBD-rich female plants. Additionally, specific phytocannabinoids and terpenoids showed an uncommon increase in concentration following fertilization with particular male plants.

Our results demonstrate that although the profile of phytocannabinoids and their relative ratios were kept, fertilization substantially decreased the concentration of nearly all phytocannabinoids in the plant regardless of the type of fertilizing male plant. Our findings may point to the functional roles of secondary metabolites in Cannabis.

Keywords: Cannabis, cannabinoids, terpenoids, secondary metabolites, chromatography/mass spectrometry, analytical methods, gas chromatography, high pressure liquid chromatography

Introduction

Cannabis sativa L. (Cannabis) has been known as a medicinal plant since ancient times.[1] During the last two decades, many studies have added to the growing evidence for its therapeutic effects in a wide range of conditions such as neurodegenerative disorders[2][3], pain[4], epilepsy,[5] multiple sclerosis[6], and more.[7] These therapeutic abilities have been attributed to the secondary metabolites biosynthesized in Cannabis[8], with more than 500 different secondary metabolites having been identified.[9][10] These metabolites belong to several groups of compounds, including phytocannabinoids, terpenoids, and flavonoids.

To date, the most characterized are phytocannabinoids, lipophilic compounds made of isoprene units (five-carbon building blocks) (Hanuš et al., 2016), which are almost exclusive to the Cannabis plant. (Gülck and Møller, 2020) More than 140 different phytocannabinoids have been found to accumulate to various extents in glandular trichomes that are located in the aerial parts of the plant and mostly on the female flowers, which are arranged in a cluster on the stem of the inflorescence.[11] Phytocannabinoids can be classified into several subclasses according to their chemical structure, including the Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) families, as well as cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC), and many others.[10][12]

Terpenoids, found in many other plants, represent a second large group of metabolites. These metabolites are closely related to phytocannabinoids, sharing the same isoprenoid precursor and built up by branched isoprene units.[13] Terpenoids are responsible for the fragrance and taste of the plant and are suggested to also have defensive roles. They may also contribute to the therapeutic effects attributed to Cannabis.[14]

Another group of metabolites worth mentioning is flavonoids. Among this group, which is widespread in the plant kingdom, there are three specific prenylated flavonoids, termed Cannflavins A, B, and C, which are unique to Cannabis and show potent anti-inflammatory abilities.[15][16][17]


References

  1. Bonini, Sara Anna; Premoli, Marika; Tambaro, Simone; Kumar, Amit; Maccarinelli, Giuseppina; Memo, Maurizio; Mastinu, Andrea (1 December 2018). "Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history" (in en). Journal of Ethnopharmacology 227: 300–315. doi:10.1016/j.jep.2018.09.004. https://linkinghub.elsevier.com/retrieve/pii/S0378874118316611. 
  2. Fernández-Ruiz, Javier (1 May 2019). "The biomedical challenge of neurodegenerative disorders: an opportunity for cannabinoid-based therapies to improve on the poor current therapeutic outcomes: Cannabinoids and neuroprotection" (in en). British Journal of Pharmacology 176 (10): 1370–1383. doi:10.1111/bph.14382. PMC PMC6487558. PMID 29856067. https://onlinelibrary.wiley.com/doi/10.1111/bph.14382. 
  3. Cassano, Tommaso; Villani, Rosanna; Pace, Lorenzo; Carbone, Antonio; Bukke, Vidyasagar Naik; Orkisz, Stanislaw; Avolio, Carlo; Serviddio, Gaetano (6 March 2020). "From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases". Frontiers in Pharmacology 11: 124. doi:10.3389/fphar.2020.00124. ISSN 1663-9812. PMC PMC7069528. PMID 32210795. https://www.frontiersin.org/article/10.3389/fphar.2020.00124/full. 
  4. Starowicz, Katarzyna; Finn, David P. (2017), "Cannabinoids and Pain: Sites and Mechanisms of Action" (in en), Advances in Pharmacology (Elsevier) 80: 437–475, doi:10.1016/bs.apha.2017.05.003, ISBN 978-0-12-811232-8, https://linkinghub.elsevier.com/retrieve/pii/S1054358917300443. Retrieved 2021-11-24 
  5. Franco, Valentina; Bialer, Meir; Perucca, Emilio (1 March 2021). "Cannabidiol in the treatment of epilepsy: Current evidence and perspectives for further research" (in en). Neuropharmacology 185: 108442. doi:10.1016/j.neuropharm.2020.108442. https://linkinghub.elsevier.com/retrieve/pii/S0028390820305104. 
  6. Rice, Jessica; Cameron, Michelle (1 August 2018). "Cannabinoids for Treatment of MS Symptoms: State of the Evidence" (in en). Current Neurology and Neuroscience Reports 18 (8): 50. doi:10.1007/s11910-018-0859-x. ISSN 1528-4042. http://link.springer.com/10.1007/s11910-018-0859-x. 
  7. Gonçalves, Joana; Rosado, Tiago; Soares, Sofia; Simão, Ana; Caramelo, Débora; Luís, Ângelo; Fernández, Nicolás; Barroso, Mário et al. (23 February 2019). "Cannabis and Its Secondary Metabolites: Their Use as Therapeutic Drugs, Toxicological Aspects, and Analytical Determination" (in en). Medicines 6 (1): 31. doi:10.3390/medicines6010031. ISSN 2305-6320. PMC PMC6473697. PMID 30813390. http://www.mdpi.com/2305-6320/6/1/31. 
  8. Andre, Christelle M.; Hausman, Jean-Francois; Guerriero, Gea (4 February 2016). "Cannabis sativa: The Plant of the Thousand and One Molecules". Frontiers in Plant Science 7: 19. doi:10.3389/fpls.2016.00019. ISSN 1664-462X. PMC PMC4740396. PMID 26870049. http://journal.frontiersin.org/Article/10.3389/fpls.2016.00019/abstract. 
  9. ElSohly, Mahmoud A.; Slade, Desmond (1 December 2005). "Chemical constituents of marijuana: The complex mixture of natural cannabinoids" (in en). Life Sciences 78 (5): 539–548. doi:10.1016/j.lfs.2005.09.011. https://linkinghub.elsevier.com/retrieve/pii/S002432050500891X. 
  10. 10.0 10.1 Flores-Sanchez, Isvett Josefina; Verpoorte, Robert (1 October 2008). "Secondary metabolism in cannabis" (in en). Phytochemistry Reviews 7 (3): 615–639. doi:10.1007/s11101-008-9094-4. ISSN 1568-7767. http://link.springer.com/10.1007/s11101-008-9094-4. 
  11. Hanuš, Lumír Ondřej; Meyer, Stefan Martin; Muñoz, Eduardo; Taglialatela-Scafati, Orazio; Appendino, Giovanni (2016). "Phytocannabinoids: a unified critical inventory" (in en). Natural Product Reports 33 (12): 1357–1392. doi:10.1039/C6NP00074F. ISSN 0265-0568. http://xlink.rsc.org/?DOI=C6NP00074F. 
  12. Berman, Paula; Futoran, Kate; Lewitus, Gil M.; Mukha, Dzmitry; Benami, Maya; Shlomi, Tomer; Meiri, David (1 December 2018). "A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis" (in en). Scientific Reports 8 (1): 14280. doi:10.1038/s41598-018-32651-4. ISSN 2045-2322. PMC PMC6155167. PMID 30250104. http://www.nature.com/articles/s41598-018-32651-4. 
  13. Booth, Judith K.; Yuen, Macaire M.S.; Jancsik, Sharon; Madilao, Lufiani L.; Page, Jonathan E.; Bohlmann, Jörg (1 September 2020). "Terpene Synthases and Terpene Variation in Cannabis sativa" (in en). Plant Physiology 184 (1): 130–147. doi:10.1104/pp.20.00593. ISSN 0032-0889. PMC PMC7479917. PMID 32591428. https://academic.oup.com/plphys/article/184/1/130-147/6117797. 
  14. Russo, Ethan B.; Marcu, Jahan (2017), "Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads" (in en), Advances in Pharmacology (Elsevier) 80: 67–134, doi:10.1016/bs.apha.2017.03.004, ISBN 978-0-12-811232-8, https://linkinghub.elsevier.com/retrieve/pii/S1054358917300273. Retrieved 2021-11-24 
  15. Radwan, Mohamed M.; ElSohly, Mahmoud A.; Slade, Desmond; Ahmed, Safwat A.; Wilson, Lisa; El-Alfy, Abir T.; Khan, Ikhlas A.; Ross, Samir A. (1 October 2008). "Non-cannabinoid constituents from a high potency Cannabis sativa variety" (in en). Phytochemistry 69 (14): 2627–2633. doi:10.1016/j.phytochem.2008.07.010. PMC PMC4888767. PMID 18774146. https://linkinghub.elsevier.com/retrieve/pii/S0031942208003518. 
  16. Rea, Kevin A; Casaretto, José A.; Al-Abdul-Wahid, M. Sameer; Sukumaran, Arjun; Geddes-McAlister, Jennifer; Rothstein, Steven J.; Akhtar, Tariq A. (1 August 2019). "Biosynthesis of cannflavins A and B from Cannabis sativa L" (in en). Phytochemistry 164: 162–171. doi:10.1016/j.phytochem.2019.05.009. https://linkinghub.elsevier.com/retrieve/pii/S0031942218303819. 
  17. Erridge, Simon; Mangal, Nagina; Salazar, Oliver; Pacchetti, Barbara; Sodergren, Mikael H. (1 October 2020). "Cannflavins – From plant to patient: A scoping review" (in en). Fitoterapia 146: 104712. doi:10.1016/j.fitote.2020.104712. https://linkinghub.elsevier.com/retrieve/pii/S0367326X2030294X. 

Notes

This presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. In some cases important information was missing from the references, and that information was added. The original article lists references in alphabetical order; however, this version lists them in order of appearance, by design.